Background: Cancer-associated fibroblasts, play a central role in the tumor-stroma interaction and promote tumorigenesis. However, it is still unclear how these processes are regulated. The aim of this study is to investigate p16 expression in cancer and stromal cells of invasive lobular carcinoma (ILC). Design: Clinicopathologic parameters and immunohistochemical stains for estrogen receptor (ER), progesterone receptor, E-cadherin, and human epidermal growth factor receptor 2 of 70 ILC cases were retrieved. In addition, immunohistochemical were performed for p53, p16, and cyclin D1. The p16 expression in cancer and stromal cells were correlated with different clinicopathologic parameters. Results: Of the 70 cases, 8 cases were p16− cancer and stromal cells, 14 cases p16− cancer and p16+ stromal cells, 14 cases p16+ cancer and p16− stromal cells, and 34 cases p16+ cancer and stromal cells. Thirty-one of the 59 cases showed axillary lymph node metastases. Nodal involvement, recurrence, and metastasis of ILC with p16+ cancer cells and p16− stromal cells were more frequent compared with other groups. ILC with p16+ cancer and p16− stromal cells were frequently negative for ER, progesterone receptor, and cyclin D1, p53 positive and triple negative compared with other groups. There was no recurrence and metastasis in ILC with p16− cancer and p16+ stromal cells. ILC with p16+ cancer and stromal cells were significantly node negative and were positive for ER and cyclin D1 compared with other groups. Conclusions: ILC with p16+ cancer and p16− stromal cells were characterized by frequent nodal involvement, recurrence, and metastatic propensity. These results suggest that p16, has novel anticancer properties capable of suppressing cancer cell migration and invasion and pharmacologic restoration of p16 level in stromal fibroblasts may be exploited as therapeutic strategy to prevent nodal or distant metastasis.

中文翻译：

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p16在癌细胞和基质细胞上的表达与小叶乳腺癌临床病理和免疫组织化学特征的相关性

背景：癌症相关成纤维细胞在肿瘤-基质相互作用中起核心作用并促进肿瘤发生。然而，目前尚不清楚如何监管这些过程。本研究的目的是研究 p16 在浸润性小叶癌 (ILC) 的癌症和基质细胞中的表达。设计：检索了 70 个 ILC 病例中雌激素受体 (ER)、孕激素受体、E-钙粘蛋白和人表皮生长因子受体 2 的临床病理参数和免疫组织化学染色。此外，还对 p53、p16 和细胞周期蛋白 D1 进行了免疫组化。癌症和基质细胞中 p16 的表达与不同的临床病理参数相关。结果：70例中，p16-癌和基质细胞8例，p16-癌和p16+基质细胞14例，p16+癌和p16-基质细胞14例，和 34 例 p16+ 癌细胞和基质细胞。59例中有31例出现腋窝淋巴结转移。与其他组相比，具有 p16+ 癌细胞和 p16- 基质细胞的 ILC 的淋巴结受累、复发和转移更频繁。与其他组相比，具有 p16+ 癌症和 p16- 基质细胞的 ILC 的 ER、孕激素受体和细胞周期蛋白 D1 经常呈阴性，p53 阳性和三阴性。在具有 p16- 癌症和 p16+ 基质细胞的 ILC 中没有复发和转移。与其他组相比，具有 p16+ 癌症和基质细胞的 ILC 显着呈淋巴结阴性，且 ER 和细胞周期蛋白 D1 呈阳性。结论：具有 p16+ 癌症和 p16- 基质细胞的 ILC 的特征在于频繁的淋巴结受累、复发和转移倾向。这些结果表明 p16、