Racial differences in the overexpression of epidermal growth factor type II receptor (HER2/neu): A major prognostic indicator in uterine serous papillary cancer

Santin, Alessandro D.; Bellone, Stefania; Siegel, Eric R.; Palmieri, Michela; Thomas, Maria; Cannon, Martin J.; Kay, Helen H.; Román, Juan José Mora; Burnett, Alexander; Pecorelli, Sërgio

doi:10.1016/j.ajog.2004.10.605

Cited by 121 publications

(96 citation statements)

References 20 publications

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“…Previous studies evaluating the HER2 status in endometrial carcinomas suffered from several limitations, including inappropriate case selection and lack of standardized HER2 testing and scoring criteria, leading to a wide range-14-80%-of reported HER2 positivity in endometrial serous carcinoma [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] (Buza et al, in press). One of the largest studies-a phase II clinical trial of singleagent trastuzumab in advanced or recurrent endometrial carcinoma-for example, has been previously criticized for including a large number of type I and mixed endometrial carcinomas, and the histological subtype was not specified in nearly half of the cases.…”

Section: Discussionmentioning

confidence: 99%

“…[14][15][16]34,35 Several previous studies used non-FDA-approved HER2 antibodies, ie, c-erbB-2 clone A0485 (DAKO), 24,35,36 c-erbB-2/ Her-2/neu Ab17 (monoclonal antibodies e2-4001 and 3B5; Neomarkers) 8 and clone TAB250 (Zymed). 16,35 Although most studies used the FDA scoring criteria for HER2 immunohistochemistry, 8,9,[13][14][15]18,22,24,30,35,36 many of them considered both the 2 þ and 3 þ immunohistochemical scores positive for HER2 overexpression. 8,13,15,30,35,36 Others used selfdeveloped semiquantitative immunohistochemical scoring systems, not currently approved for any other tumor types.…”

Section: Discussionmentioning

confidence: 99%

“…[4][5][6][7] Although HER2/neu has been studied in endometrial cancer for over 15 years, standard testing methods or scoring guidelines are yet to be developed. The reported rates of HER2 overexpression in endometrial serous carcinoma range between 14 and 80%, due to-at least in part-the significant variation in the HER2 testing methods, interpretation and scoring criteria used [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] (Buza et al, in press).…”

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Toward standard HER2 testing of endometrial serous carcinoma: 4-year experience at a large academic center and recommendations for clinical practice

et al. 2013

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HER2 overexpression and/or amplification have been reported in endometrial serous carcinoma, suggesting that HER2 may be a promising therapeutic target. However, there is considerable variation in the reported rates of HER2 overexpression and amplification, likely-at least in part-resulting from variability in the testing methods, interpretation, and scoring criteria used. Unlike in breast and gastric cancer, currently there are no established guidelines for HER2 testing in endometrial carcinoma. A total of 108 endometrial carcinoma cases-85 pure serous carcinomas and 23 mixed endometrial carcinomas with serous component-were identified over a 4-year period. All H&E and HER2 immunohistochemical slides were reviewed and HER2 FISH results (available on 52 cases) were retrieved from pathology reports. HER2 immunohistochemical scores were assigned according to the FDA criteria and the current breast ASCO/CAP scoring criteria. Clinical information was retrieved from the patients' medical records. Thirty-eight cases (35%) showed HER2 overexpression and/or gene amplification, 20 of which (53%) had significant heterogeneity of protein expression by immunohistochemistry. Lack of apical membrane staining resulting in a lateral/basolateral staining pattern was observed in the majority of HER2-positive tumors. Five of the HER2-positive cases (13%) demonstrated discrepant immunohistochemical scores when using the FDA versus ASCO/CAP scoring system. The overall concordance rate between HER2 immunohistochemistry and FISH was 75% (39/52) when using the FDA criteria, compared with 81% (42/52) by the ASCO/CAP scoring system. In conclusion, in this largest comprehensive study, 35% of endometrial serous carcinoma harbors HER2 protein overexpression and/or gene amplification, over half of which demonstrate significant heterogeneity of protein expression. The current breast ASCO/CAP scoring criteria provide the highest concordance between immunohistochemistry and FISH. Assessment of HER2 immunohistochemistry on multiple tumor sections or sections with large tumor areas is recommended, due to the significant heterogeneity of HER2 protein expression. Keywords: endometrial serous carcinoma; fluorescent in situ hybridization; HER2 testing; heterogeneity; immunohistochemistry The significance of human epidermal growth factor receptor 2 (HER2/Neu, ERBB2) amplification and HER2 protein overexpression has been well established in the pathogenesis and targeted therapy of breast cancer and more recently in gastric and gastroesophageal junction carcinomas. 1-3 Tumorspecific HER2 testing guidelines have been developed to reflect the unique biological features of each of these tumor types and to predict the clinical response to HER2-targeted therapy. [4][5][6][7] Although HER2/neu has been studied in endometrial cancer for over 15 years, standard testing methods or scoring guidelines are yet to be developed. The reported rates of HER2 overexpression in endometrial serous carcinoma range between 14 and 80%, due to-at least in part-the significant ...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Toward standard HER2 testing of endometrial serous carcinoma: 4-year experience at a large academic center and recommendations for clinical practice

et al. 2013

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“…Results from clinical trials, with uniform eligibility requirements and treatment, also show poorer outcomes for black women, suggesting unknown biologic differences in hosts or tumors (8). Consistent with differences in histologic types, endometrial tumors in black women have less favorable molecular features (9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 92%

The Impact of Race and Comorbidity on Survival in Endometrial Cancer

Olson

Atoria

Coté

et al. 2012

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Poorer survival from endometrial cancer in blacks than in whites is well documented. The aims of this study were to determine whether diabetes, hypertension, or other conditions influence survival and whether accounting for these conditions reduces this racial disparity.Methods: Using the SEER-Medicare database, we investigated the influence of diabetes, hypertension, and other comorbid conditions on survival in black and white women age 66 with endometrial cancer. We used Cox proportional hazards regression to evaluate the influence of comorbidities on survival for blacks and whites separately and to study survival differences between blacks and whites after adjustment for diabetes, hypertension, and other medical conditions, as well as for demographics, tumor characteristics, and treatment.Results: In both racial subgroups, women with diabetes or other conditions had poorer overall survival, whereas hypertensive black women experienced better survival [HR, 0.74; 95% confidence interval (CI), 0.60-0.92]. For disease-specific survival, diabetes was associated with poorer survival in white women (HR, 1.19; 95% CI, 1.06-1.35) but not in blacks (HR, 0.97; 95% CI, 0.73-1.30); hypertension and other conditions were not significantly related to survival. After adjustment, black women had poorer survival than white women, with HRs of 1.16 (95% CI, 1.05-1.28) for overall and 1.27 (95% CI, 1.08-1.49) for disease-specific survival.Conclusions: Diabetes influences disease-specific survival in white women but not in blacks. The racial disparity in survival is not explained by the presence of other health conditions. Impact: Further research should focus on the unknown factors that lead to poorer survival in black women compared with whites. Cancer Epidemiol Biomarkers Prev; 21(5); 753-60. Ó2012 AACR.

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“…HER2 status of an endometrial tumor has been shown to be an independent prognostic indicator as HER2 overexpression was associated with a poor overall survival and a very low relapse-free survival time. Therefore, HER2 has been considered a candidate marker of worse overall prognosis in endometrial cancer (Santin et al 2005, Benevolo et al 2007. Although, overexpression of HER2 helps to predict both prognosis and chemoresistance inspite of that the use of Herceptin (trastuzumab), a monoclonal antibody directed against HER2, for the therapy of patients with HER2 positive endometrial tumors should be further investigated in clinical trials (Slomovitz et al 2004a).…”

Section: The Egfr Pathwaymentioning

confidence: 99%

Resistance to chemotherapy and hormone therapy in endometrial cancer

Chaudhry¹,

Asselin²

2009

Endocrine-Related Cancer

112

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Endometrial cancer is the most common gynecological malignancy in developed countries and represents the eighth leading cause of cancer related death in women. The growing incidence of endometrial cancer leads scientists and oncologists to identify effective preventive measures and also molecular markers for diagnosis and prognosis. Chemotherapy and hormone therapy is the mainstay treatment option for advanced and recurrent endometrial cancer and response to therapy is one of the most important factor which favors prognosis and overall survival. In recent years, there have been major advances in the treatment of patients with endometrial cancer. Despite advances made in the treatment of this cancer, the overall survival of patients has not significantly improved because considerable number of patients harbor tumor refractory to these therapies and the majority of the initially responsive tumors become refractory to treatments. Therefore, determination of sensitivity/resistance is becoming increasingly important for individualization of endometrial cancer therapy. The aim of this review is to present the existing knowledge about the molecular markers that could play a crucial role in determining resistance to chemo-and hormone therapy. Extensive literature search for the cell signaling pathways and factors responsible for chemoresistance have been performed and reviewed. Several recent studies suggest that deregulations in the apoptotic pathways (such as p53, Fas/FasL, Bcl-2 family proteins, inhibitor of apoptosis proteins), survival pathways (PI3K/AKT, MAPK), hormone receptor signaling pathways (progesterone receptor), Cyclooxygenase-2 and Her-2 are considered as key factors involved in the onset and maintenance of therapeutic resistance, suggesting that resistance is a multi-factorial phenomenon.

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Racial differences in the overexpression of epidermal growth factor type II receptor (HER2/neu): A major prognostic indicator in uterine serous papillary cancer

Cited by 121 publications

References 20 publications

Toward standard HER2 testing of endometrial serous carcinoma: 4-year experience at a large academic center and recommendations for clinical practice

Toward standard HER2 testing of endometrial serous carcinoma: 4-year experience at a large academic center and recommendations for clinical practice

The Impact of Race and Comorbidity on Survival in Endometrial Cancer

Resistance to chemotherapy and hormone therapy in endometrial cancer

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