Computational development of a molecular-based approach to improve risk stratification of endometrial cancer patients.

Bruno Casali,Alessia Ciarrocchi,Valentina Mastrofilippo,Giovanni Battista La Sala,Enrico Farnetti,Davide Nicoli,Raffaella Zamponi,Riccardo Bellazzi,Vincenzo Dario Mandato,Federica Torricelli

doi:10.18632/oncotarget.25354

Abstract

Histological classification and staging are the gold standard for the prognosis of endometrial cancer (EC). However, in morphologically intermediate and doubtful cases this approach results largely insufficient, defining the need for better classification criteria.In this work we developed an algorithm that based on EC genetic alterations and in combination with the current histological classification, improves EC patients prognostic stratification, in particular in doubtful cases. A panel of 26 cancer related genes was analyzed in 89 EC patients and somatic functional mutations were investigated in association with different histology and outcome.An unsupervised hierarchical clustering analysis revealed that two groups of patients with different tumor grade and different prognosis can be distinguished by mutational profile. In particular, the mutational status of APC, CTNNB1, PIK3CA, PTEN, SMAD4 and TP53 resulted to be principal drivers of prognostic clustering. Consistently, a decisional tree generated by a data mining approach summarizes the consequential molecular criteria for patients prognostic stratification.The model proposed by this work provides the clinician with a tool able to support the prognosis of EC patients and consequently drives the choice of the most appropriated therapeutic strategy and follow up.

Highlights

Endometrial cancer (EC) is the most common gynecological cancer in industrialized countries
According to Federation of Gynaecology and Obstetrics (FIGO) classification, 13 tumors were staged as IA, 36 as IB, 17 as IC; eight patients were staged as II, 14 as III (5 IIIA, 1 IIIB and 8 IIIC) and one as IV
To date histological characterization and staging are the gold standard for endometrial cancer (EC) prognosis

Summary

Introduction

Endometrial cancer (EC) is the most common gynecological cancer in industrialized countries. The early onset of symptoms explains why, at the time of the diagnosis, 70% of the patients present an early-stage disease, far resulting in a favorable prognosis with 77% 5-year overall survival rate (OS). Type 1 ECs are endometrioid cancer, associated with hyperestrogeneism and typically preceded by endometrial hyperplasia. They are often diagnosed at an early stage, www.oncotarget.com and have a good prognosis. Type 2 EC includes nonendometrioid cancers such as serous, clear cell, mixed cell, undifferentiated and carcinosarcoma. These neoplasms not estrogens correlated, often occur in the presence of an atrophic endometrium and have a poor prognosis. The 5-year OS rate of patients with endometrioid adenocarcinoma (type 1) range from 75% to 86%, in contrast to 50% to 60% of patients with non-endometrioid cancer (type 2)

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Conclusion