Serine protease inhibitor Kazal type 1 and epidermal growth factor receptor are expressed in pancreatic tubular adenocarcinoma, intraductal papillary mucinous neoplasm, and pancreatic intraepithelial neoplasia
Serine protease inhibitor Kazal type 1 and epidermal growth factor receptor are expressed in pancreatic tubular adenocarcinoma, intraductal papillary mucinous neoplasm, and pancreatic intraepithelial neoplasia
复制标题
DOI：
10.1007/s00534-012-0587-6
复制
发表时间：
2013-08-01
影响因子：
3
通讯作者：
Baba, Hideo
中科院分区：
文献类型：
--
作者：
Ozaki, Nobuyuki;Ohmuraya, Masaki;Baba, Hideo
丝氨酸蛋白酶抑制剂Kazal 1型（SPINK 1）在正常人胰腺腺泡细胞和多种肿瘤中表达，并与表皮生长因子受体（EGFR）结合，通过胰腺癌细胞系中的丝裂原活化蛋白激酶级联介导细胞增殖。在此，我们旨在评估SPINK 1和EGFR在各种肿瘤性病变中的表达，包括显示癌前病变的组织。胰腺导管腺癌的手术标本（n = 23），导管内乳头状粘液性肿瘤（IPMN; n = 21），导管腺癌以外的胰腺肿瘤（n = 8），慢性胰腺炎（n = 11），对胰腺上皮内瘤变（PanIN）的SPINK 1和EGFR表达进行免疫组化分析，共鉴定出PanIN-1A型65例，PanIN-1B型32例，PanIN-2型17例，PanIN-3型6例。SPINK 1和EGFR在几乎所有PanIN病变中均表达。所有管状导管腺癌、IPMN和粘液性囊腺癌样本（导管起源的肿瘤）均表达SPINK 1，而腺泡细胞癌、未分化癌、腺鳞癌、胰岛素瘤和胰岛细胞癌则不表达。EGFR在87%的管状腺癌和48%的IPMN病变中表达。在IPMN病变中，恶性病变（IPMC）比良性病变（IPMA）更常表达EGFR。EGFR在正常胰管和慢性胰腺炎病变的胰管复合体中呈散在表达，提示SPINK 1在胰腺导管腺癌和胰腺肿瘤中作为生长因子，通过EGFR信号通路发挥作用，EGFR参与了胰腺导管腺癌和胰腺肿瘤的恶性转化。
Serine protease inhibitor Kazal type 1 (SPINK1) is expressed in normal human pancreatic acinar cells and in a variety of tumors, and binds to the epidermal growth factor receptor (EGFR), mediating cell proliferation through the mitogen-activated protein kinase cascade in pancreatic cancer cell lines. Here, we aimed to assess SPINK1 and EGFR expression in various neoplastic lesions, including tissues demonstrating precancerous changes.Surgical specimens of pancreatic ductal adenocarcinoma (n = 23), intraductal papillary mucinous neoplasm (IPMN; n = 21), pancreatic neoplasms other than ductal adenocarcinoma (n = 8), chronic pancreatitis (n = 11), and pancreatic intraepithelial neoplasia (PanIN) lesions within the resected specimens were analyzed immunohistochemically for SPINK1 and EGFR expression.Sixty-five PanIN-1A, 32 PanIN-1B, 17 PanIN-2, and 6 PanIN-3 were identified. Both SPINK1 and EGFR were expressed in almost all PanIN lesions. All tubular ductal adenocarcinoma, IPMN, and mucinous cystadenocarcinoma samples (neoplasms of ductal origin) expressed SPINK1, whereas acinar cell carcinoma, anaplastic carcinoma, adenosquamous carcinoma, insulinoma, and islet cell carcinoma did not. EGFR was expressed in 87 % of tubular adenocarcinoma and 48 % of IPMN lesions. Among IPMN lesions, malignant lesions (IPMC) expressed EGFR more often than benign lesions (IPMA) did. Scattered expression of EGFR was observed in normal pancreatic ducts and within the tubular complex within chronic pancreatitis lesions.These results indicate that SPINK1 plays a role as a growth factor, signaling through the EGFR pathway in pancreatic ductal adenocarcinoma and neoplasms, and that the EGFR is involved in the malignant transformation of IPMN.