Oestrogen receptor beta isoform expression in sporadic colorectal cancer, familial adenomatous polyposis and progressive stages of colorectal cancer

Author(s):Show less -

Stevanato Filho, Paulo Roberto ^{[1, 2]} ; Aguiar Junior, Samuel ^[1] ; Begnami, Maria Dirlei ^[3] ; Kuasne, Hellen ^{[4, 5, 6]} ; Spencer, Ranyell Matheus ^[1] ; Nakagawa, Wilson Toshihiko ^[1] ; Bezerra, Tiago Santoro ^[1] ; Kupper, Bruna Catin ^[1] ; Takahashi, Renata Maymi ^[1] ; Barros Filho, Mateus ^[4] ; Rogatto, Silvia Regina ^{[4, 5, 6]} ; Lopes, Ademar ^[1]

Affiliation

^[1] AC Camargo Canc Ctr, Colorectal Tumor Nucleus, Pelv Surg Dept, Sao Paulo, SP - Brazil

^[2] AC Camargo Canc Ctr, Colorectal Tumor Nucleus, R Prof Antonio Prudente, 211 Liberdade, BR-01509010 Sao Paulo, SP - Brazil

^[3] AC Camargo Canc Ctr, Dept Pathol, Sao Paulo, SP - Brazil

^[4] AC Camargo Canc Ctr, CIPE Int Ctr Res, Sao Paulo, SP - Brazil

^[5] Vejle Sygehus, Dept Clin Genet, Vejle - Denmark

^[6] Univ Southern Denmark, Inst Reg Hlth Res, Odense - Denmark

• Document type: Journal article
• Source: BMC CANCER; v. 17, NOV 13 2017.
• Web of Science Citations: 1

Abstract

Background: Among the sex hormones, oestrogen may play a role in colorectal cancer, particularly in conjunction with oestrogen receptor-beta (ER beta). The expression of ER beta isoform variants and their correlations with familial adenomatous polyposis (FAP) syndrome and sporadic colorectal carcinomas are poorly described. Methods: This study aimed to investigate the expression levels of the ER beta 1, ER beta 2, ER beta 4 and ER beta 5 isoform variants using quantitative RT-PCR (921 analyses) in FAP, normal mucosa, adenomatous polyps and sporadic colorectal carcinomas. Results: Decreased expression of ER beta isoforms was identified in sporadic polyps and in sporadic colorectal cancer as well as in polyps from FAP syndrome patients compared with normal tissues (p < 0.001). In FAP patients, ER beta 1 and ER beta 5 isoforms showed significant down-expression in polyps (p < 0.001) compared with matched normal tissues. However, no differences were observed when sporadic colorectal carcinomas were compared to normal mucosa tissues. These findings suggest an association of the ER beta isoform variants in individuals affected by germline mutations of the APC gene. Progressively decreased expression of ER beta was found in polyps at early stages of low-grade dysplasia, followed by T1-T2 and T3-T4 tumours (p < 0.05). In sporadic colorectal cancer, the loss of expression was an independent predictor of recurrence, and ER beta 1 and ER beta 5 expression levels were associated with better disease-free survival (p = 0.002). Conclusion: These findings may provide a better understanding of oestrogens and their potential preventive and therapeutic effects on sporadic colorectal cancer and cancers associated with FAP syndrome. (AU)

• FAPESP's process: 08/57887-9 - National Institute of Oncogenomics
• Grantee: Luiz Paulo Kowalski
• Support Opportunities: Research Projects - Thematic Grants