Molecular biomarkers predicting early development of endometrial carcinoma: A pilot study

• Published in: European journal of cancer care Vol. 28; no. 6; pp. e13137 - n/a
• Main Authors: Lupini, Laura, Scutiero, Gennaro, Iannone, Piergiorgio, Martinello, Ruby, Bassi, Cristian, Ravaioli, Noemi, Soave, Ilaria, Bonaccorsi, Gloria, Lanza, Giovanni, Gafà, Roberta, Loizzi, Vera, Negrini, Massimo, Greco, Pantaleo
• Format: Journal Article
• Language: English
• Published: England Hindawi Limited 01-11-2019
• Subjects: Adenomatous polyposis coli; Aged; Biomarkers; Biomarkers, Tumor - genetics; Biopsy; Cancer; cancer gene mutations; Carcinoma; Carcinoma, Endometrioid - diagnosis; Carcinoma, Endometrioid - genetics; Cdc4 protein; DNA Mutational Analysis; Early Detection of Cancer; Endometrial cancer; Endometrial Neoplasms - diagnosis; Endometrial Neoplasms - genetics; Endometrium; Female; Gene sequencing; Genes; Genes, Neoplasm - genetics; Humans; Malignancy; Middle Aged; Mutation; Neoplasm Staging; Nursing; p53 Protein; Pilot Projects; Prognosis; PTEN protein; Retrospective Studies; Survival; TOR protein; Tumor suppressor genes; Tumors; Uterine cancer; Uterus; endometrial cancer; biomarkers; cancer gene mutations
• ISSN: 0961-5423; 1365-2354
• DOI: 10.1111/ecc.13137

Objective
Endometrial carcinoma represents the most common gynaecological cancer and the sixth most frequent cancer among women worldwide. The 5‐year survival of patients with stage I endometrial carcinoma is 75%–88% versus 50% for stage III or 15% for stage IV disease. Therefore, early detection could improve survival rates. Specifically, in the most prevalent, type 1 endometrial cancer develops from hyperplastic endometrium. The aim of the study was to evaluate the utility of cancer gene mutations from endometrial biopsies towards predicting synchronous or metachronous development of malignant lesions. The aim of the study was to evaluate whether endometrial biopsies could already carry mutations in cancer genes useful for predicting or anticipating subsequent cancer development.
Methods
Patients with a previous endometrial biopsy negative for cancer, followed by a subsequent biopsy positive for cancer, were included in the study. A fifty cancer genes targeted next‐generation sequencing panel were used to investigate mutations in matched non‐cancerous and malignant samples.
Results
All biopsies from cancer tissues harboured mutations in one or more of the following genes: APC, CTNNB1, FBXW7, HNF1A, KRAS, MTOR, NRAS, PIK3CA, PTEN, RB1 and TP53. Additionally, 50% of the biopsies from matched non‐cancerous tissues exhibited mutations in PTEN, KRAS or PIK3CA genes.
Conclusions
These results suggest that detecting pathogenic mutations in oncogenes or tumour suppressor genes in an otherwise benign condition is associated with a risk of developing a malignant disease. Given the identification of mutations several months or years before the appearance of a malignancy, our finding suggests that a closer monitoring of patients who present such molecular alterations in non‐cancerous uterine mass is warranted.