Expression of chromogranin A,B and BRCA1 in breast carcinoma

家族性乳腺和卵巢肿瘤抑制基因BRCA 1编码一个1863个氨基酸的蛋白质。BRCA 1序列中的功能域在BRCA 1的第1214-1223位氨基酸处具有完全一致的颗粒蛋白。BRCA 1定位于乳腺上皮和分泌蛋白。乳腺癌中存在神经内分泌分化的现象，可通过嗜银反应或颗粒蛋白免疫组化检测。BRCA 1抑制肿瘤的机制尚不清楚。乳腺癌颗粒素表达的临床意义。也很清楚采用免疫组化方法研究了正常人和乳腺癌组织中嗜铬粒蛋白A（CgA）、嗜铬粒蛋白B（Cg B）和BRCA 1的组织定位。以揭示BRCA 1和颗粒蛋白的表达之间是否存在任何关系。在CA。BRCA I在非侵袭性导管癌中的阳性率为100%。浸润性导管癌88%。BRCA 1免疫反应性丧失占总病例的12%。包括11例家族性病例的I型。CgA和CgB不一定共表达。70%的非浸润性导管癌中可见CgA阳性细胞。浸润性导管癌占23%，CgB阳性率为65%。浸润性导管癌占39%。颗粒蛋白的免疫反应性是异质性的，不同于BRCA 1。对生长抑素2A型受体（sstr）进行了免疫组化和mRNA原位杂交研究。约60%的乳腺癌呈sstr免疫反应阳性，并同时表达雌激素受体。sstr表达与肿瘤大小、淋巴结转移无关。BRCA 1作为肿瘤抑制因子的可能机制可能部分与通过颗粒蛋白和颗粒蛋白加工的一些肽的sstr有关。

The familial breast and ovarian tumor suppressor gene BRCA 1 encodes an 1863amino acid protein, The functional domains in the BRCA 1 sequence have perfect granin consensus at BRCA 1 amino acids 1214-1223. BRCA 1 localizes to mamary epthelium and secretary protein. There have been recognized that there are breast carcinomas(ca) with neuroendocrine (NE) differentiation detected by argyrophilic reaction or granin immunostaining. The mechanism of tumor suppression by BRCA 1 is not clarified. The clilnical significance of expression of granins in breast ca. is alsounclear. We immunohistochemically investigated tissue localization of chromogranin A(CgA), chromogranin B (CgB) and BRCA 1 in normal and ca. of the mammary gland to reveal if there is any relationship between expression of BRCA 1 and granins. In the ca. tissues, BRCA I was observed in 100% of noninvasive ductal ca.. and in 88%of invasive ductal ca.. Loss of BRCA 1 immunoreactivity was 12% in the total ca. including I of 11 familial cases. CgA and CgB were not necessarily coexpressed. The cells immunoreactive for CgA were observed in 70% of noninvasive ductal ca. and 23%of invasive ductal ca., and those for CgB were 65% of noninvasive ductal ca. and 39%of invasive ductal ca.. The immunoreactivity of granins was heterogenous and different from that of BRCA 1. With regards to somatostatin receptor type 2A (sstr), we investigated immunohistochemically and also on mRNA using in situ hybridizationmethod. About 60% of breast carcinomas showed sstr immunoreactivity and coexpressed estrogen receptor. Expression of sstr had little correlation to the tumorsize, lymph node metastasis. The possible mechanism of BRCA 1 as a tumor suppressor may relate in part to sstr through granins and some peptides processed from granins.