Immunohistochemical characterisation of molecular subtypes in endometrial cancer

被引：0

作者：

Lapinska-Szumczyk, Sylwia M. ^{[1
]}

Supernat, Anna M. ^{[2
,3
]}

Majewska, Hanna I. ^{[4
]}

Gulczynski, Jacek ^{[5
]}

Biernat, Wojciech ^{[4
]}

Wydra, Dariusz ^{[1
]}

Zaczek, Anna J. ^{[2
,3
]}

机构：

[1] Med Univ Gdansk, Dept Gynaecol Gynaecol Oncol & Gynaecol Endocrino, Klin 1a, PL-80402 Gdansk, Poland

[2] Univ Gdansk, Dept Med Biotechnol, Intercollegiate Fac Biotechnol, PL-80211 Gdansk, Poland

[3] Med Univ Gdansk, PL-80211 Gdansk, Poland

[4] Med Univ Gdansk, Dept Pathomorphol, PL-80214 Gdansk, Poland

[5] Med Acad Gdansk, Dept Pathol & Neuropathol, PL-80211 Gdansk, Poland

来源：

INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE | 2015年 / 8卷 / 11期

关键词：

Molecular subtypes; ERBB/PI3K pathway; Mismatch Repair system; TP53; endometrial cancer; MISMATCH REPAIR DEFICIENCY; PROGNOSTIC-FACTOR; BREAST-CANCER; EXPRESSION; CARCINOMA; P53; PI3K; PATHWAY; ASSOCIATION; SURVIVAL;

D O I：

暂无

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Four molecular subtypes have lately been established in endometrial cancer basing on estrogen receptor (ER), progesterone receptor (PR) and HER2 status: ER+/PR+/HER2+, ER+/PR+/HER2-, ER-/PR-/HER2+ and ER-/PR-/HER2-. The subtypes have shown diversity in terms of prognosis, clinicopathological and molecular characteristics, with ER+/PR+/HER2- and ER-/PR-/HER2+ group exhibiting exceptionally benign and aggressive behavior, respectively. We have further characterized the subtypes in the context of pathways known to drive endometrial carcinogenesis: phosphatidylinositol 3-kinase (PI3K)-AKT pathway (ERBB/PI3K pathway), TP53 system, and the mismatch repair (MMR) mechanism. Analysis of tumor heterogeneity was also included. ER+/PR+/HER2+ was characterized by active ERBB/PI3K pathway occurring in 58% of cases. Subtype ER-/PR-/HER2+ was characterized by the most frequent TP53 mutations (83% of cases). Triple negative phenotype utterly lacked active ERBB/PI3K pathway. Analyzed major pathways rarely correlated with clinicopathologial data but mutated TP53 and retained MMR did correlate with shorter overall survival (both P<0.01). The presence of tumor heterogeneity was most frequent in ER-/PR-/HER2+ subtype (53% of all cases). The presented results further emphasize that the molecular subtype distinction, along with MMR and TP53 status, could be a useful diagnostic tool in guiding individualized therapy.

引用

页码：21981 / +

页数：14

共 36 条

[1]

Allred DC, 1998, MODERN PATHOL, V11, P155

[2] Microsatellite instability and hMLH1 and hMSH2 expression in renal tumors [J].

Altavilla, Giuseppe ;

Fassan, Matteo ;

Busatto, Graziella ;

Orsolan, Martina ;

Giacomelli, Luciano .

ONCOLOGY REPORTS, 2010, 24 (04) :927-932

[3] Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK): Explanation and Elaboration [J].

Altman, Douglas G. ;

McShane, Lisa M. ;

Sauerbrei, Willi ;

Taube, Sheila E. .

PLOS MEDICINE, 2012, 9 (05)

[4] p53 Regulates insulin-like growth factor-I receptor gene expression in uterine serous carcinoma and predicts responsiveness to an insulin-like growth factor-I receptor-directed targeted therapy [J].

Attias-Geva, Zohar ;

Bentov, Itay ;

Kidron, Dvora ;

Amichay, Keren ;

Sarfstein, Rive ;

Fishman, Ami ;

Bruchim, Ilan ;

Werner, Haim .

EUROPEAN JOURNAL OF CANCER, 2012, 48 (10) :1570-1580

[5] Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies [J].

Barba, C ;

Cavalli-Sforza, T ;

Cutter, J ;

Darnton-Hill, I ;

Deurenberg, P ;

Deurenberg-Yap, M ;

Gill, T ;

James, P ;

Ko, G ;

Miu, AH ;

Kosulwat, V ;

Kumanyika, S ;

Kurpad, A ;

Mascie-Taylor, N ;

Moon, HK ;

Nishida, C ;

Noor, MI ;

Reddy, KS ;

Rush, E ;

Schultz, JT ;

Seidell, J ;

Stevens, J ;

Swinburn, B ;

Tan, K ;

Weisell, R ;

Wu, ZS ;

Yajnik, CS ;

Yoshiike, N ;

Zimmet, P .

LANCET, 2004, 363 (9403) :157-163

[6] p53 in breast cancer subtypes and new insights into response to chemotherapy [J].

Bertheau, Philippe ;

Lehmann-Che, Jacqueline ;

Varna, Mariana ;

Dumay, Anne ;

Poirot, Brigitte ;

Porcher, Raphael ;

Turpin, Elisabeth ;

Plassa, Louis-Francois ;

de Roquancourt, Anne ;

Bourstyn, Edwige ;

de Cremoux, Patricia ;

Janin, Anne ;

Giacchetti, Sylvie ;

Espie, Marc ;

de The, Hugues .

BREAST, 2013, 22 :S27-S29

[7] Cutoff Finder: A Comprehensive and Straightforward Web Application Enabling Rapid Biomarker Cutoff Optimization [J].

Budczies, Jan ;

Klauschen, Frederick ;

Sinn, Bruno V. ;

Gyoerffy, Balazs ;

Schmitt, Wolfgang D. ;

Darb-Esfahani, Silvia ;

Denkert, Carsten .

PLOS ONE, 2012, 7 (12)

[8] HER2/neu in Endometrial Cancer A Promising Therapeutic Target With Diagnostic Challenges [J].

Buza, Natalia ;

Roque, Dana M. ;

Santin, Alessandro D. .

ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE, 2014, 138 (03) :343-350

[9] Activation of PI3K/Akt/mTOR Pathway and Dual Inhibitors of PI3K and mTOR in Endometrial Cancer [J].

Chen, Jiezhong ;

Zhao, Kong-Nan ;

Li, Rui ;

Shao, Renfu ;

Chen, Chen .

CURRENT MEDICINAL CHEMISTRY, 2014, 21 (26) :3070-3080

[10] Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up [J].

Colombo, N. ;

Preti, E. ;

Landoni, F. ;

Carinelli, S. ;

Colombo, A. ;

Marini, C. ;

Sessa, C. .

ANNALS OF ONCOLOGY, 2013, 24 :33-38

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