HISTOPATHOLOGICAL RESEARCH OF CARCINOGENESIS OF DUCTAL CARCINOMA IN SITU

Research Project

Project/Area Number	14570134
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	Human pathology
Research Institution	GUNMA UNIVERSITY
Principal Investigator	OYAMA Tetsunari GUNMA UNIVERSITY, SCHOOL OF MEDICINE, DEPT. OF PATHOLOGY, ASSOCIATE PROFESSOR, 医学部, 助教授 (50233622)
Co-Investigator(Kenkyū-buntansha)	SANO Takaaki GUNMA UNIVERSITY, SCHOOL OF MEDICINE, DEPT. OF PATHOLOGY, ASSISTANT PROFESSOR, 医学部, 講師 (90292581)
Project Period (FY)	2002 – 2003
Project Status	Completed (Fiscal Year 2003)
Budget Amount *help	¥1,400,000 (Direct Cost: ¥1,400,000) Fiscal Year 2003: ¥500,000 (Direct Cost: ¥500,000) Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000)
Keywords	BREAST CANCER / 14-3-3 SIGUMA PROTEIN / CARCINOGENESIS / ATYPICAL CYSTIC LOBULES / HORMONE RECEPTOR / CCHA / 非浸潤性乳管癌 / 病理 / 異型乳管過形成 / AIB1
Research Abstract	It becomes more important to clarify the molecular pathological mechanism of early carcinogenesis and identify the morphological change of breast cancer according to the increase of occurrence of breast cancer. We have already proposed "atypical cystic lobules (ACL)", which is also called as columnar cell hyperplasia with atypia (CCHA). It is one type of early change of low grade ductal carcinoma in situ (DCIS). In this study, we carried out immunohistochemical analysis of breast carcinogens using several antibodies for related proteins, including hormone receptor (Estrogen receptor), hormone related protein (Estrogen-responsive RING finger protein) and 14-3-3 sigma (σ) protein. We have studied the expression of these proteins in usual ductal hyperplasia (UDH), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). Immunostaining for estrogen receptor alpha (ERα), p53 and (Efp) was also carried out. Immunohistochemically, expression of 14-3-3σ was seen in 92% UDH lesions and gradually decreased from 65% in DCIS to 23% in IDC. The expression of ERα decreased gradually from UDH to DCIS to IDC, while p53 showed an inverse staining pattern to that of ERα. The expression of Efp showed no significant difference among the three breast lesions. Hence, the present immunohistochemical study confirmed 14-3-3σ as a tumor suppressor in breast carcinogenesis. A similar immunohistochemical analysis was then carried out on columnar cell hyperplasia with atypia (CCHA), in which the expression pattern of tumor suppressor 14-3-3σ, ERα and p53 suggested that the possibility may exist that CCHA is a pre-cancerous lesions.