Expression of chromogranin A,B and BRCA1 in breast carcinoma

家族性乳腺癌和卵巢癌抑制基因BRCA-1编码一个1863个氨基酸的蛋白质，BRCA-1序列的功能域在BRCA-1的1214-1223位氨基酸之间具有完美的Granin一致性。BRCA-1定位于哺乳动物上皮细胞和分泌蛋白。人们已经认识到，通过嗜银反应或颗粒免疫染色发现有神经内分泌(NE)分化的乳腺癌。BRCA-1抑制肿瘤的机制尚不清楚。颗粒素在乳腺癌中表达的临床意义也不清楚。本文应用免疫组织化学方法研究了嗜铬颗粒蛋白A(CgA)、嗜铬颗粒蛋白B(Cgb)和BRCA-1在正常乳腺和癌旁组织中的定位，以揭示BRCA-1的表达与颗粒蛋白之间的关系。在癌组织中，BRCA I在100%的非侵袭性导管癌中表达。在88%的侵袭性导管癌中。BRCA-1免疫反应缺失占总病例数的12%，包括11例家族性病例。CgA和Cgb不一定共表达。CgA在70%的非侵袭性导管癌和23%的浸润性导管癌中呈阳性表达，在65%的非侵袭性导管癌和39%的浸润性导管癌中呈阳性表达。对于生长抑素受体2A型(Sstr)，我们用免疫组织化学和原位杂交的方法研究了其mRNA的表达。约60%的乳腺癌表达sSTR免疫反应并共表达雌激素受体。Sstr的表达与肿瘤大小、淋巴结转移关系不大。BRCA-1抑制肿瘤的可能机制可能部分与SSTR通过颗粒物或颗粒物加工的某些多肽有关。

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.