Umeda Tomoko, Ishida Mitsuaki, Murata Satoshi, Mori Tsuyoshi, Kawai Yuki, Itoi Naoko, Tomida Kaori, Tanaka Akie, Sakai Sachiko, Kitamura Mina, Kubota Yoshihiro, Kushima Ryoji, Tani Masaji
Department of Surgery, Shiga University of Medical Science, Tsukinowa-cho, Seta, Otsu, Shiga, 520-2192, Japan.
Department of Clinical Laboratory Medicine and Division of Diagnostic Pathology, Shiga University of Medical Science, Tsukinowa-cho, Seta, Otsu, Shiga, 520-2192, Japan.
Breast Cancer. 2016 Nov;23(6):869-875. doi: 10.1007/s12282-015-0653-4. Epub 2015 Oct 22.
Invasive micropapillary carcinoma (IMPC) is a distinct histopathological variant of breast carcinoma and frequently develops lymph node metastases. CD44 is a family of transmembrane glycoprotein receptors with multiple variant isoforms (CD44v), which have tissue-specific expression. Previous studies have demonstrated a loss or gain of CD44v and CD44 standard form (CD44s) expression in breast carcinomas. In this study, we analyzed the immunoprofiles of CD44s, CD44v6, and CD44v9 in IMPC and compared them with those in a concurrent invasive carcinoma of no special type (ICNST) component, thus clarifying the significance of CD44 expression in IMPC.
Twenty-one consecutive cases of mixed IMPC were included in this study. The expression statuses of CD44s, CD44v6, and CD44v9 in both the IMPC and ICNST components were analyzed semiquantitatively by immunohistochemistry.
The immunohistochemical scores of CD44s, CD44v6, and CD44v9 were significantly decreased in the IMPC component compared to the ICNST component (p = 0.00335 for CD44s, p = 0.000982 for CD44v6, and p = 0.00271 for CD44v9). Moreover, the immunohistochemical scores of CD44v6 in the IMPC component and CD44v9 in the ICNST component of lymph node metastasis cases were significantly lower compared to cases without lymph node metastasis (p < 0.01).
Decreased CD44 expression may play an important role in promoting lymph node metastasis in IMPC through an inability or decreased capacity to bind with the surrounding stroma. Moreover, high CD44s expression levels in the concurrent ICNST component may be related to the development of IMPC.
浸润性微乳头状癌(IMPC)是乳腺癌一种独特的组织病理学变体,常发生淋巴结转移。CD44是一类具有多种变异体同工型(CD44v)的跨膜糖蛋白受体家族,其具有组织特异性表达。既往研究已证实乳腺癌中CD44v和CD44标准型(CD44s)表达存在缺失或增加。在本研究中,我们分析了IMPC中CD44s、CD44v6和CD44v9的免疫表型,并将其与同时存在的非特殊类型浸润性癌(ICNST)成分进行比较,从而阐明CD44表达在IMPC中的意义。
本研究纳入21例连续的混合性IMPC病例。通过免疫组织化学对IMPC和ICNST成分中CD44s、CD44v6和CD44v9的表达状态进行半定量分析。
与ICNST成分相比,IMPC成分中CD44s、CD44v6和CD44v9的免疫组织化学评分显著降低(CD44s,p = 0.00335;CD44v6,p = 0.000982;CD44v9,p = 0.00271)。此外,与无淋巴结转移的病例相比,淋巴结转移病例的IMPC成分中CD44v6和ICNST成分中CD44v9的免疫组织化学评分显著更低(p < 0.01)。
CD44表达降低可能通过与周围基质结合能力丧失或降低在促进IMPC淋巴结转移中起重要作用。此外,同时存在的ICNST成分中高CD44s表达水平可能与IMPC的发生有关。