Ohori N P, Coppola D, Landreneau R J
Department of Pathology, Montefiore-University of Pittsburgh Medical Center, Pennsylvania 15213-2582, USA.
Mod Pathol. 1996 May;9(5):507-12.
CD44 is a family of transmembrane glycoproteins involved in cell-to-cell and cell-to-matrix interactions. Of the CD44 isoforms characterized, the v6 variant has been shown to confer metastatic potential in animal models and its expression has been correlated with aggressive behavior in some human malignancies. In an attempt to provide further insight into the heterogeneous appearance and behavior of bronchioloalveolar carcinomas (BACs), the pattern of CD44v6 staining in five mucinous, five nonmucinous, and eight sclerosing stage I BACs were compared with 12 comparably staged conventional pulmonary adenocarcinomas (CPAs). Formalin-fixed, paraffin-embedded sections were stained with monoclonal antibodies to CD44v6 (clone VFF-7). Neoplastic goblet cells, whether growing in a lepidic pattern in mucinous BACs or in an invasive pattern in CPAs, consistently demonstrated low level expression of CD44v6. In contrast, lepidic growth by neoplastic cells of type 2 pneumocyte or Clara cell differentiation demonstrated high levels in five of five cases of nonmucinous BACs, seven of eight cases of sclerosing BACs, and six of nine cases of CPAs. Similar cells of type 2 pneumocyte or Clara cell differentiation within the scarred area of sclerosing BAC demonstrated an intermediate degree of staining with four of eight cases marking with high levels, whereas none of the nine cases of CPAs with invasion by these cells showed high levels in the desmoplastic areas. From these results, two patterns of CD44v6 expression were recognized in BACs and CPAs. First, the expression appeared to be partly dependent on differentiation as cells demonstrating mucinous differentiation, whether in BACs or CPAs, consistently lacked CD44v6 staining. Second, in cells of type pneumocyte or Clara cell differentiation the expression was dependent on the growth pattern and their relationship to the stroma. High level expression was noted in neoplastic cells growing in a lepidic pattern, whereas those demonstrating invasion gradually lost the expression with increasing degrees of stromal reaction. Thus, the expression of CD44v6 in pulmonary BACs and similarly staged CPAs appears to be different from other human malignancies that have a positive correlation with aggressive behavior.
CD44是一族参与细胞间和细胞与基质相互作用的跨膜糖蛋白。在所鉴定的CD44亚型中，v6变体在动物模型中已显示出具有转移潜能，并且其表达与某些人类恶性肿瘤的侵袭性行为相关。为了进一步深入了解细支气管肺泡癌（BAC）的异质性外观和行为，将5例黏液性、5例非黏液性和8例硬化性I期BAC的CD44v6染色模式与12例分期相当的传统肺腺癌（CPA）进行了比较。用针对CD44v6的单克隆抗体（克隆VFF-7）对福尔马林固定、石蜡包埋的切片进行染色。肿瘤性杯状细胞，无论是在黏液性BAC中呈鳞屑样生长还是在CPA中呈浸润性生长，始终显示出CD44v6的低水平表达。相反，2型肺细胞或 Clara细胞分化的肿瘤细胞呈鳞屑样生长，在5例非黏液性BAC中的5例、8例硬化性BAC中的7例以及9例CPA中的6例中显示出高水平表达。硬化性BAC瘢痕区域内类似的2型肺细胞或 Clara细胞分化的细胞显示出中等程度的染色，8例中有4例为高水平染色，而9例被这些细胞侵袭的CPA中，在促纤维增生区域均未显示出高水平表达。从这些结果中，在BAC和CPA中识别出两种CD44v6表达模式。首先，表达似乎部分依赖于分化，因为显示黏液性分化的细胞，无论是在BAC还是CPA中，始终缺乏CD44v6染色。其次，在2型肺细胞或 Clara细胞分化的细胞中，表达依赖于生长模式及其与基质的关系。在呈鳞屑样生长的肿瘤细胞中观察到高水平表达，而那些显示浸润的细胞随着基质反应程度的增加逐渐失去表达。因此，肺BAC和分期相当的CPA中CD44v6的表达似乎与其他与侵袭性行为呈正相关的人类恶性肿瘤不同。
