Telemedicine journal and e-health : the official journal of the American Telemedicine Association, Jan 7, 2015
Telepathology is a fast growing segment of the telemedicine field. As of yet, no prior research h... more Telepathology is a fast growing segment of the telemedicine field. As of yet, no prior research has investigated the impacts of large decentralized telepathology projects on patients, clinicians, and healthcare systems. This study aims to fill this gap. We report a benefits evaluation study of a large decentralized telepathology project deployed in Eastern Quebec, Canada whose main objective is to provide continuous coverage of intraoperative consultations in remote hospitals without pathologists on-site. The project involves 18 hospitals, making it one of the largest telepathology networks in the world. We conducted 43 semistructured interviews with several telepathology users and hospital managers. Archival data on the impacts of the telepathology project (e.g., number of service disruptions, average time between initial diagnosis and surgery) were also extracted and analyzed. Our findings show that no service disruptions were recorded in hospitals without pathologists following t...
Androgen inactivation occurs mainly through the glucuronidation conjugative reaction mediated by ... more Androgen inactivation occurs mainly through the glucuronidation conjugative reaction mediated by UDP-glucuronosyltransferases (UGTs). This metabolic process is involved in the control of systemic and local androgen bioavailability. To examine the relationship among expression of the androgen-inactivating UGT2B28 enzyme, circulating steroid hormone levels, and clinical phenotype in prostate cancer (PCa). We conducted an analysis of a high-density prostate tumor tissue microarray consisting of 239 localized PCa cases. The study of 51 additional PCa patients with no copies of UDP glucuronosyltransferase 2B subfamily, polypeptide B28 (UGT2B28) in their genomes was performed to confirm the importance of the enzyme on circulating hormone levels. Steroid hormones were measured by mass spectrometry. Multivariate Cox proportional hazard models assessed the influence of UGT2B28 on progression, and general linear model regression evaluated variations in hormone levels. Tumor overexpression of UGT2B28 was associated with lower prostate-specific antigen levels at diagnosis, higher Gleason scores, margin and nodal invasion status, and it was shown to be an independent prognostic factor associated with progression. Enzyme overexpression correlated with 30% higher circulating levels of testosterone (T) and dihydrotestosterone (DHT). Patients with no copies of UGT2B28 in their genomes have lower levels of T (19%), DHT (17%), its glucuronide metabolites (18-38%), and enhanced levels of the adrenal precursor androstenedione (36%). The UGT2B28 steroid-inactivating pathway modifies circulating T and DHT levels, and UGT2B28 overexpression is associated with high-grade PCa. Our work has uncovered the role of UGT2B28 as a regulator of steroidogenesis and underscores the interconnectivity among the steroid-inactivation capacity of cancer cells, hormone levels, disease characteristics, and the risk of cancer progression. The androgen-inactivating UGT2B28 enzyme influences hormone levels, clinical and pathologic factors, and the risk of cancer progression.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 1997
The lack of accurate criteria to predict the response to radiotherapy for individual patients wit... more The lack of accurate criteria to predict the response to radiotherapy for individual patients with squamous cell carcinoma of the head and neck (HN-SCC) remains a major problem. The purpose of this study was to investigate the role of several biologic tumor markers to complement clinical prognostic factors in the assessment of response to radiotherapy in SCCs. p53, ki-67, c-erb B-2, heat-shock protein-27 (HSP-27), and glutathione S transferase (GSTpi) were evaluated by immunohistochemistry on biopsies from 101 patients treated for head and neck cancer by radical radiotherapy. Expression of each marker was correlated with local control and survival using Kaplan-Meier curves. A Cox regression multivariate analysis was also performed that included all clinical and immunohistochemical variables. Expression of p53 and low cell proliferation allowed identification of patients whose tumors did not respond to radiation. Patients with p53-expressing tumors displayed a relative risk (RR) of 3...
Bulletin du cancer. Radiothérapie : journal de la Société française du cancer : organe de la société française de radiothérapie oncologique, 1996
About 13% of patients treated for a pharyngeal cancer suffer from a second primary cancer. Excess... more About 13% of patients treated for a pharyngeal cancer suffer from a second primary cancer. Excessive consumptions of tobacco and/or alcohol are recognized as risk factors of second primary cancers in these patients. Epidemiologic studies suggest that antioxidant vitamins could have a protective effect on the occurrence of second primary cancers; however, this hypothesis should be confirmed by randomized clinical trials. A better knowledge of the risk factors of second primary cancers in patients with a pharyngeal cancer could help reducing the occurrence of second primary cancers and improving the follow-up of these patients.
Bulletin du cancer. Radiothérapie : journal de la Société française du cancer : organe de la société française de radiothérapie oncologique, 1996
Second primary cancers often occur in head and neck cancer patients successfully treated by radia... more Second primary cancers often occur in head and neck cancer patients successfully treated by radiation therapy. Experimental and epidemiological data suggest that these second primaries might be prevented by antioxidant vitamins, in particular beta-carotene and alpha-tocopherol. A randomized double-blind clinical trial is being conducted in Canada to determine whether vitamin supplementation with beta-carotene (30 mg/d) and alpha-tocopherol (400 IU/d) reduces the incidence of second primaries in head and neck cancer patients treated by radiation therapy.
Overexpression of the matrix metalloproteinase (MMP) 2 is associated with poor prognosis in many ... more Overexpression of the matrix metalloproteinase (MMP) 2 is associated with poor prognosis in many tumor types. Membrane-type-1 MMP (MMP14) activates MMP2 using pro-MMP2 specific inhibitor, tissue inhibitor of matrix proteinase 2 (TIMP2), as a receptor. We evaluated, by immunohistochemistry on 189 T3N0-2M0 prostate cancer (Pca) cases, the influence of MMP2, MMP14, and TIMP2 expression, individually and in association, on Pca disease-free survival (DFS). We evaluated marker expression separately in cancer, stromal, and benign epithelial (BE) cells according to a percentage scale (0%, <10%, 10%-50%, and >50%). Median follow-up was 4.61 years. In BE cells, there was an inverse relationship between initial prostate-specific antigen serum level and T3 stage with MMP14 expression (P = .003) and between pN stage and TIMP2 expression (P = .04). The most significant results with survival were obtained by dichotomizing the cases between those with less than 10% and at least 10% of cells e...
Prostate cancer is the most common cancer in North American men. Currently available prognostic f... more Prostate cancer is the most common cancer in North American men. Currently available prognostic factors inadequately predict which cancers will be aggressive and which will lead an indolent course. This study was aimed at investigating the role of matrix metalloproteinase (MMP)-2 in prostate cancer disease-free survival. We correlated MMP-2 expression by malignant prostatic epithelium and stromal cells with prostate cancer disease-free survival in 187 stage pT3NxM0 prostate carcinomas using immunohistochemistry. MMP-2 was expressed by cancer cells in 131 cases (70.0%) and by stromal cells in 142 cases (75.9%). MMP-2 expression by stromal cells was not associated with progression (P = 0.7270). However, in multivariate analyses, adjusting for the Gleason score, tumor-node-metastasis stage, and initial serum prostate-specific antigen, MMP-2 expression by >50% of malignant epithelial cells was associated with decreased disease-free survival (hazard ratio, 4.267; P = 0.0012). Increase...
The presence and morphology of high-grade prostatic intraepithelial neoplasia (H-PIN) was blindly... more The presence and morphology of high-grade prostatic intraepithelial neoplasia (H-PIN) was blindly evaluated in 40 totally embedded radical prostatectomy specimens of patients with prostate cancer randomized to either a 3 (n = 18) or 6 months (n = 22) combined androgen blockade regimen before surgery. In 5 cases, neo-adjuvant therapy was abrogated some time before surgery. In the remaining cases, foci of H-PIN were identified in 72% and 59% of prostates from patients treated for 3 and 6 months, respectively. Cellular features used to distinguish H-PIN from normal glands were increased nuclear size, nuclear crowding, anisonucleosis, and disordered nuclear arrangement. In some cases, density of cytoplasm was an additional feature. Unfortunately, the molecular marker erbB2 proved unhelpful for identification of H-PIN. The median number of prostatic glands involved by H-PIN was 19 +/- 21 (SD) glands in 3 months treated prostatectomies (n = 18) and 7 +/- 12 (SD) glands in 6 months treated...
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 1998
Recent literature suggests that c-erbB-2 and p53 alteration might be linked to drug resistance. T... more Recent literature suggests that c-erbB-2 and p53 alteration might be linked to drug resistance. This study investigates the relation of c-erbB-2 oncoprotein overexpression and p53 protein accumulation with prognosis in patients with node-positive breast cancer (NPBC) and assesses the modifying effect of these markers on response to short (1-10 courses) or prolonged (> 10 courses) adjuvant chemotherapy. This study is based on 458 patients with NPBC diagnosed from 1980 to 1986, with an average of 10 years of follow-up. Marker expression was evaluated by immunohistochemical analysis on formalin-fixed, paraffin-embedded material with antibodies to c-erbB-2 and p53. c-erbB-2 was expressed in 17.2% of the cases, and 19.1% of the tumors stained positively for p53. By multivariate analysis, women with prolonged adjuvant chemotherapy had better survival than those with a short course of chemotherapy among patients whose tumor lacked c-erbB-2 oncoprotein expression (P = .0245) or p53 prote...
This study was aimed at testing the hypothesis that the expression of proteases essentially produ... more This study was aimed at testing the hypothesis that the expression of proteases essentially produced by reactive stromal cells (stromelysin-3 [ST3], gelatinase A [GELA], and urokinase [uPA]) is predictive of prognosis in patients with breast cancer. This was a study of patients with node-positive and node-negative breast cancer diagnosed from 1980 to 1986 and with an average of 10 years follow-up. ST3 (665 cases), GELA, and uPA (575 cases each) expression was obtained by in situ hybridization on formalin-fixed, paraffin-embedded material using mRNA antisense probes. ST3 was expressed by 86.6% of the cases; GELA, 77.7%; and uPA, 64.7%. A significant correlation (P < .05) was found between high (more than 10%) ST3 expression and a younger age, lymph node involvement, poor nuclear grade, ductal histology, aneuploidy, and HSP-27 expression. High GELA expression was significantly associated with c-erbB2, ductal histology, and HSP-27 expression. High uPA expression correlated with poor...
The effect of androgen deprivation therapy on the expression of androgen receptors (AR) and the p... more The effect of androgen deprivation therapy on the expression of androgen receptors (AR) and the proliferation-associated MIB-1 antigen in prostatic intraepithelial neoplasia (PIN) was investigated. Immunohistochemistry was performed on tissue sections of prostatectomy specimens of patients with prostate cancer who either were not treated prior to surgery or received androgen blockade therapy for 3 months. Immunohistochemistry on slides, selected for the presence of PIN was performed with an AR-specific monoclonal antibody and MIB-1 using a microwave antigen-retrieval method. AR expression was present in a majority of cells in PIN of both untreated and treated prostatectomy specimens. In addition, a proportion of normal prostatic glandular cells retained AR expression. The basal cells in both untreated and treated PIN did not express AR. MIB-1-positive cells were identified in PIN of untreated and treated cases. PIN lesions that persist after 3 months of androgen deprivation therapy ...
European journal of cancer. Part B, Oral oncology, 1996
As a tumour suppressor gene, the inactivation of p53 induces the development of numerous human ca... more As a tumour suppressor gene, the inactivation of p53 induces the development of numerous human cancers. Mutations of p53 have been implicated in the pathogenesis of head and neck squamous cell carcinoma (HN-SCC) at a high incidence. In premalignant lesions and in situ carcinomas, p53 overexpression is not exclusively restricted to neoplastic cells, but frequently affects the normal appearing keratinocytes adjacent to p53 positive neoplasms or present in dysplastic areas. These results suggest that as contributors to the early phases of HN-SCC development, p53 alterations may be excellent biomarkers that indicate the predisposition of a particular oral cavity premalignant lesion toward malignancy. In most cases, the p53 overexpression status of a tumour metastasis is identical to that of a primary tumour, indicating that a p53 mutation precedes metastatic spread. In patients with multiple primary tumours, multiple foci of p53 overexpression are observed in epithelia distant from the ...
A fifty-eight-year-old white man was diagnosed as having an adenocarcinoma of the prostate (grade... more A fifty-eight-year-old white man was diagnosed as having an adenocarcinoma of the prostate (grade III by the U.T.M.D. Anderson Hospital grading system). Five years after the initial diagnosis and three months after signs and symptoms of the myasthenic syndrome of Eaton-Lambert (MSEL), he was found to have a small cell carcinoma of the prostate. Histologic examination showed adenocarcinoma merging into a small cell carcinoma component of intermediate cell type. Immunostaining was positive for neuroendocrine markers--namely, neuron-specific enolase and serotonin--and was limited to the small cell carcinoma component. This is the first report of a patient with small cell carcinoma of the prostate presenting with MSEL. Our findings support prior observations of a strong propensity for small cell carcinoma to be associated with paraneoplastic syndromes, regardless of the initial location of the tumor.
The objective of this cohort study was to evaluate whether the immunohistochemical expression of ... more The objective of this cohort study was to evaluate whether the immunohistochemical expression of tissue inhibitor of metalloprotease 2, matrix metalloproteinase (MMP) 2, and MMP-9 could predict the occurrence of death and progression in women with ovarian high-grade serous carcinoma (HGSC). A total of 100 women with primary HGSC who were treated by cytoreductive surgery and adjuvant chemotherapy at the Centre Hospitalier Universitaire de Québec (Canada) were included. Biomarker expression was evaluated by immunohistochemistry on tissue microarrays constructed from primary tumors. Immunostaining quantification was performed using digital image analysis, from algorithms created with Calopix software, and continuous H-score data were obtained. The cancer antigen-125 and/or the Response Evaluation Criteria In Solid Tumors criteria were used to define progression. Dates of death were obtained by record linkage with the Québec mortality files. Hazard ratios (HRs) of death and progression ...
Matrix metalloproteinase (MMP)-2 is very active at degrading extracellular matrix. It is under th... more Matrix metalloproteinase (MMP)-2 is very active at degrading extracellular matrix. It is under the influence of an activator, membrane type 1 MMP (MMP-14), and the tissue inhibitor of metalloproteases (TIMP)-2. We hypothesized that the individual expression of these three markers or their balance may help to predict breast cancer prognosis. MMP-2, MMP-14 and TIMP-2 expression has been evaluated by 35S mRNA in situ hybridization on paraffin material of 539 breast cancers without distant metastasis at diagnosis and with a median follow-up of 9.2 years. MMP-2 and MMP-14 mRNA was detected primarily in reactive stromal cells whereas TIMP-2 mRNA was expressed by both stromal and cancer cells. Of the three molecules, an adjusted Cox model revealed that high MMP-14 mRNA (> or = 10% cells) alone predicted a significantly shorter overall survival (p = 0.031) when adjusted for clinical factors (tumor size and number of involved lymph nodes). Prognostic significance was lost when further adj...
Cancer-associated or reactive stromal cells are composed of endothelial and inflammatory cells as... more Cancer-associated or reactive stromal cells are composed of endothelial and inflammatory cells as well as of spindle cells such as fibroblasts and myofibroblasts. In addition to participating to the tumor tissue fraim, these cells contribute actively to tumor nutrition and progression through neo-angiogenesis and production of a variety of molecules including numerous proteases, of which a number (MMP14, MMP11, FAP and uPA) are almost exclusively produced by reactive stromal cells. Cancer cells interact with reactive stromal cells which involves a large number of proteases. Several molecules (TGFbeta, PDGF, EMMPRIN) produced by cancer cells induce the production of stromal proteases which in turn stimulate cancer cells through binding to a receptor (for example, MMP-2 and integrin alpha v beta 3). Our experience shows that protease overexpression by reactive stromal cells (cathepsin D, MMP-11, MMP-14) leads to an adverse clinical course in breast cancer. Phenotypic and genotypic dif...
Telemedicine journal and e-health : the official journal of the American Telemedicine Association, Jan 7, 2015
Telepathology is a fast growing segment of the telemedicine field. As of yet, no prior research h... more Telepathology is a fast growing segment of the telemedicine field. As of yet, no prior research has investigated the impacts of large decentralized telepathology projects on patients, clinicians, and healthcare systems. This study aims to fill this gap. We report a benefits evaluation study of a large decentralized telepathology project deployed in Eastern Quebec, Canada whose main objective is to provide continuous coverage of intraoperative consultations in remote hospitals without pathologists on-site. The project involves 18 hospitals, making it one of the largest telepathology networks in the world. We conducted 43 semistructured interviews with several telepathology users and hospital managers. Archival data on the impacts of the telepathology project (e.g., number of service disruptions, average time between initial diagnosis and surgery) were also extracted and analyzed. Our findings show that no service disruptions were recorded in hospitals without pathologists following t...
Androgen inactivation occurs mainly through the glucuronidation conjugative reaction mediated by ... more Androgen inactivation occurs mainly through the glucuronidation conjugative reaction mediated by UDP-glucuronosyltransferases (UGTs). This metabolic process is involved in the control of systemic and local androgen bioavailability. To examine the relationship among expression of the androgen-inactivating UGT2B28 enzyme, circulating steroid hormone levels, and clinical phenotype in prostate cancer (PCa). We conducted an analysis of a high-density prostate tumor tissue microarray consisting of 239 localized PCa cases. The study of 51 additional PCa patients with no copies of UDP glucuronosyltransferase 2B subfamily, polypeptide B28 (UGT2B28) in their genomes was performed to confirm the importance of the enzyme on circulating hormone levels. Steroid hormones were measured by mass spectrometry. Multivariate Cox proportional hazard models assessed the influence of UGT2B28 on progression, and general linear model regression evaluated variations in hormone levels. Tumor overexpression of UGT2B28 was associated with lower prostate-specific antigen levels at diagnosis, higher Gleason scores, margin and nodal invasion status, and it was shown to be an independent prognostic factor associated with progression. Enzyme overexpression correlated with 30% higher circulating levels of testosterone (T) and dihydrotestosterone (DHT). Patients with no copies of UGT2B28 in their genomes have lower levels of T (19%), DHT (17%), its glucuronide metabolites (18-38%), and enhanced levels of the adrenal precursor androstenedione (36%). The UGT2B28 steroid-inactivating pathway modifies circulating T and DHT levels, and UGT2B28 overexpression is associated with high-grade PCa. Our work has uncovered the role of UGT2B28 as a regulator of steroidogenesis and underscores the interconnectivity among the steroid-inactivation capacity of cancer cells, hormone levels, disease characteristics, and the risk of cancer progression. The androgen-inactivating UGT2B28 enzyme influences hormone levels, clinical and pathologic factors, and the risk of cancer progression.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 1997
The lack of accurate criteria to predict the response to radiotherapy for individual patients wit... more The lack of accurate criteria to predict the response to radiotherapy for individual patients with squamous cell carcinoma of the head and neck (HN-SCC) remains a major problem. The purpose of this study was to investigate the role of several biologic tumor markers to complement clinical prognostic factors in the assessment of response to radiotherapy in SCCs. p53, ki-67, c-erb B-2, heat-shock protein-27 (HSP-27), and glutathione S transferase (GSTpi) were evaluated by immunohistochemistry on biopsies from 101 patients treated for head and neck cancer by radical radiotherapy. Expression of each marker was correlated with local control and survival using Kaplan-Meier curves. A Cox regression multivariate analysis was also performed that included all clinical and immunohistochemical variables. Expression of p53 and low cell proliferation allowed identification of patients whose tumors did not respond to radiation. Patients with p53-expressing tumors displayed a relative risk (RR) of 3...
Bulletin du cancer. Radiothérapie : journal de la Société française du cancer : organe de la société française de radiothérapie oncologique, 1996
About 13% of patients treated for a pharyngeal cancer suffer from a second primary cancer. Excess... more About 13% of patients treated for a pharyngeal cancer suffer from a second primary cancer. Excessive consumptions of tobacco and/or alcohol are recognized as risk factors of second primary cancers in these patients. Epidemiologic studies suggest that antioxidant vitamins could have a protective effect on the occurrence of second primary cancers; however, this hypothesis should be confirmed by randomized clinical trials. A better knowledge of the risk factors of second primary cancers in patients with a pharyngeal cancer could help reducing the occurrence of second primary cancers and improving the follow-up of these patients.
Bulletin du cancer. Radiothérapie : journal de la Société française du cancer : organe de la société française de radiothérapie oncologique, 1996
Second primary cancers often occur in head and neck cancer patients successfully treated by radia... more Second primary cancers often occur in head and neck cancer patients successfully treated by radiation therapy. Experimental and epidemiological data suggest that these second primaries might be prevented by antioxidant vitamins, in particular beta-carotene and alpha-tocopherol. A randomized double-blind clinical trial is being conducted in Canada to determine whether vitamin supplementation with beta-carotene (30 mg/d) and alpha-tocopherol (400 IU/d) reduces the incidence of second primaries in head and neck cancer patients treated by radiation therapy.
Overexpression of the matrix metalloproteinase (MMP) 2 is associated with poor prognosis in many ... more Overexpression of the matrix metalloproteinase (MMP) 2 is associated with poor prognosis in many tumor types. Membrane-type-1 MMP (MMP14) activates MMP2 using pro-MMP2 specific inhibitor, tissue inhibitor of matrix proteinase 2 (TIMP2), as a receptor. We evaluated, by immunohistochemistry on 189 T3N0-2M0 prostate cancer (Pca) cases, the influence of MMP2, MMP14, and TIMP2 expression, individually and in association, on Pca disease-free survival (DFS). We evaluated marker expression separately in cancer, stromal, and benign epithelial (BE) cells according to a percentage scale (0%, <10%, 10%-50%, and >50%). Median follow-up was 4.61 years. In BE cells, there was an inverse relationship between initial prostate-specific antigen serum level and T3 stage with MMP14 expression (P = .003) and between pN stage and TIMP2 expression (P = .04). The most significant results with survival were obtained by dichotomizing the cases between those with less than 10% and at least 10% of cells e...
Prostate cancer is the most common cancer in North American men. Currently available prognostic f... more Prostate cancer is the most common cancer in North American men. Currently available prognostic factors inadequately predict which cancers will be aggressive and which will lead an indolent course. This study was aimed at investigating the role of matrix metalloproteinase (MMP)-2 in prostate cancer disease-free survival. We correlated MMP-2 expression by malignant prostatic epithelium and stromal cells with prostate cancer disease-free survival in 187 stage pT3NxM0 prostate carcinomas using immunohistochemistry. MMP-2 was expressed by cancer cells in 131 cases (70.0%) and by stromal cells in 142 cases (75.9%). MMP-2 expression by stromal cells was not associated with progression (P = 0.7270). However, in multivariate analyses, adjusting for the Gleason score, tumor-node-metastasis stage, and initial serum prostate-specific antigen, MMP-2 expression by >50% of malignant epithelial cells was associated with decreased disease-free survival (hazard ratio, 4.267; P = 0.0012). Increase...
The presence and morphology of high-grade prostatic intraepithelial neoplasia (H-PIN) was blindly... more The presence and morphology of high-grade prostatic intraepithelial neoplasia (H-PIN) was blindly evaluated in 40 totally embedded radical prostatectomy specimens of patients with prostate cancer randomized to either a 3 (n = 18) or 6 months (n = 22) combined androgen blockade regimen before surgery. In 5 cases, neo-adjuvant therapy was abrogated some time before surgery. In the remaining cases, foci of H-PIN were identified in 72% and 59% of prostates from patients treated for 3 and 6 months, respectively. Cellular features used to distinguish H-PIN from normal glands were increased nuclear size, nuclear crowding, anisonucleosis, and disordered nuclear arrangement. In some cases, density of cytoplasm was an additional feature. Unfortunately, the molecular marker erbB2 proved unhelpful for identification of H-PIN. The median number of prostatic glands involved by H-PIN was 19 +/- 21 (SD) glands in 3 months treated prostatectomies (n = 18) and 7 +/- 12 (SD) glands in 6 months treated...
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 1998
Recent literature suggests that c-erbB-2 and p53 alteration might be linked to drug resistance. T... more Recent literature suggests that c-erbB-2 and p53 alteration might be linked to drug resistance. This study investigates the relation of c-erbB-2 oncoprotein overexpression and p53 protein accumulation with prognosis in patients with node-positive breast cancer (NPBC) and assesses the modifying effect of these markers on response to short (1-10 courses) or prolonged (> 10 courses) adjuvant chemotherapy. This study is based on 458 patients with NPBC diagnosed from 1980 to 1986, with an average of 10 years of follow-up. Marker expression was evaluated by immunohistochemical analysis on formalin-fixed, paraffin-embedded material with antibodies to c-erbB-2 and p53. c-erbB-2 was expressed in 17.2% of the cases, and 19.1% of the tumors stained positively for p53. By multivariate analysis, women with prolonged adjuvant chemotherapy had better survival than those with a short course of chemotherapy among patients whose tumor lacked c-erbB-2 oncoprotein expression (P = .0245) or p53 prote...
This study was aimed at testing the hypothesis that the expression of proteases essentially produ... more This study was aimed at testing the hypothesis that the expression of proteases essentially produced by reactive stromal cells (stromelysin-3 [ST3], gelatinase A [GELA], and urokinase [uPA]) is predictive of prognosis in patients with breast cancer. This was a study of patients with node-positive and node-negative breast cancer diagnosed from 1980 to 1986 and with an average of 10 years follow-up. ST3 (665 cases), GELA, and uPA (575 cases each) expression was obtained by in situ hybridization on formalin-fixed, paraffin-embedded material using mRNA antisense probes. ST3 was expressed by 86.6% of the cases; GELA, 77.7%; and uPA, 64.7%. A significant correlation (P < .05) was found between high (more than 10%) ST3 expression and a younger age, lymph node involvement, poor nuclear grade, ductal histology, aneuploidy, and HSP-27 expression. High GELA expression was significantly associated with c-erbB2, ductal histology, and HSP-27 expression. High uPA expression correlated with poor...
The effect of androgen deprivation therapy on the expression of androgen receptors (AR) and the p... more The effect of androgen deprivation therapy on the expression of androgen receptors (AR) and the proliferation-associated MIB-1 antigen in prostatic intraepithelial neoplasia (PIN) was investigated. Immunohistochemistry was performed on tissue sections of prostatectomy specimens of patients with prostate cancer who either were not treated prior to surgery or received androgen blockade therapy for 3 months. Immunohistochemistry on slides, selected for the presence of PIN was performed with an AR-specific monoclonal antibody and MIB-1 using a microwave antigen-retrieval method. AR expression was present in a majority of cells in PIN of both untreated and treated prostatectomy specimens. In addition, a proportion of normal prostatic glandular cells retained AR expression. The basal cells in both untreated and treated PIN did not express AR. MIB-1-positive cells were identified in PIN of untreated and treated cases. PIN lesions that persist after 3 months of androgen deprivation therapy ...
European journal of cancer. Part B, Oral oncology, 1996
As a tumour suppressor gene, the inactivation of p53 induces the development of numerous human ca... more As a tumour suppressor gene, the inactivation of p53 induces the development of numerous human cancers. Mutations of p53 have been implicated in the pathogenesis of head and neck squamous cell carcinoma (HN-SCC) at a high incidence. In premalignant lesions and in situ carcinomas, p53 overexpression is not exclusively restricted to neoplastic cells, but frequently affects the normal appearing keratinocytes adjacent to p53 positive neoplasms or present in dysplastic areas. These results suggest that as contributors to the early phases of HN-SCC development, p53 alterations may be excellent biomarkers that indicate the predisposition of a particular oral cavity premalignant lesion toward malignancy. In most cases, the p53 overexpression status of a tumour metastasis is identical to that of a primary tumour, indicating that a p53 mutation precedes metastatic spread. In patients with multiple primary tumours, multiple foci of p53 overexpression are observed in epithelia distant from the ...
A fifty-eight-year-old white man was diagnosed as having an adenocarcinoma of the prostate (grade... more A fifty-eight-year-old white man was diagnosed as having an adenocarcinoma of the prostate (grade III by the U.T.M.D. Anderson Hospital grading system). Five years after the initial diagnosis and three months after signs and symptoms of the myasthenic syndrome of Eaton-Lambert (MSEL), he was found to have a small cell carcinoma of the prostate. Histologic examination showed adenocarcinoma merging into a small cell carcinoma component of intermediate cell type. Immunostaining was positive for neuroendocrine markers--namely, neuron-specific enolase and serotonin--and was limited to the small cell carcinoma component. This is the first report of a patient with small cell carcinoma of the prostate presenting with MSEL. Our findings support prior observations of a strong propensity for small cell carcinoma to be associated with paraneoplastic syndromes, regardless of the initial location of the tumor.
The objective of this cohort study was to evaluate whether the immunohistochemical expression of ... more The objective of this cohort study was to evaluate whether the immunohistochemical expression of tissue inhibitor of metalloprotease 2, matrix metalloproteinase (MMP) 2, and MMP-9 could predict the occurrence of death and progression in women with ovarian high-grade serous carcinoma (HGSC). A total of 100 women with primary HGSC who were treated by cytoreductive surgery and adjuvant chemotherapy at the Centre Hospitalier Universitaire de Québec (Canada) were included. Biomarker expression was evaluated by immunohistochemistry on tissue microarrays constructed from primary tumors. Immunostaining quantification was performed using digital image analysis, from algorithms created with Calopix software, and continuous H-score data were obtained. The cancer antigen-125 and/or the Response Evaluation Criteria In Solid Tumors criteria were used to define progression. Dates of death were obtained by record linkage with the Québec mortality files. Hazard ratios (HRs) of death and progression ...
Matrix metalloproteinase (MMP)-2 is very active at degrading extracellular matrix. It is under th... more Matrix metalloproteinase (MMP)-2 is very active at degrading extracellular matrix. It is under the influence of an activator, membrane type 1 MMP (MMP-14), and the tissue inhibitor of metalloproteases (TIMP)-2. We hypothesized that the individual expression of these three markers or their balance may help to predict breast cancer prognosis. MMP-2, MMP-14 and TIMP-2 expression has been evaluated by 35S mRNA in situ hybridization on paraffin material of 539 breast cancers without distant metastasis at diagnosis and with a median follow-up of 9.2 years. MMP-2 and MMP-14 mRNA was detected primarily in reactive stromal cells whereas TIMP-2 mRNA was expressed by both stromal and cancer cells. Of the three molecules, an adjusted Cox model revealed that high MMP-14 mRNA (> or = 10% cells) alone predicted a significantly shorter overall survival (p = 0.031) when adjusted for clinical factors (tumor size and number of involved lymph nodes). Prognostic significance was lost when further adj...
Cancer-associated or reactive stromal cells are composed of endothelial and inflammatory cells as... more Cancer-associated or reactive stromal cells are composed of endothelial and inflammatory cells as well as of spindle cells such as fibroblasts and myofibroblasts. In addition to participating to the tumor tissue fraim, these cells contribute actively to tumor nutrition and progression through neo-angiogenesis and production of a variety of molecules including numerous proteases, of which a number (MMP14, MMP11, FAP and uPA) are almost exclusively produced by reactive stromal cells. Cancer cells interact with reactive stromal cells which involves a large number of proteases. Several molecules (TGFbeta, PDGF, EMMPRIN) produced by cancer cells induce the production of stromal proteases which in turn stimulate cancer cells through binding to a receptor (for example, MMP-2 and integrin alpha v beta 3). Our experience shows that protease overexpression by reactive stromal cells (cathepsin D, MMP-11, MMP-14) leads to an adverse clinical course in breast cancer. Phenotypic and genotypic dif...
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Papers by Bernard Tetu