Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University 3-1-1 Maidashi, Fukuoka, 812-8582, Japan.
Hum Pathol. 2010 Nov;41(11):1507-15. doi: 10.1016/j.humpath.2010.02.019. Epub 2010 Jul 24.
Intraductal papillary mucinous neoplasm is characterized by cystically dilated main and/or branch pancreatic duct with mucus. According to the degree of atypia, intraductal papillary mucinous neoplasm is classified into 3 groups: adenoma, borderline, and carcinoma. Furthermore, intraductal papillary mucinous neoplasm is considered to progress through an adenoma-carcinoma sequence like colorectal carcinoma. Programmed cell death 4 is a recently identified tumor suppressor that was found to inhibit translation. Programmed cell death 4 has been reported to inhibit tumorigenesis, tumor progression, proliferation, invasion, and metastasis in several human malignancies. We examined 108 cases of intraductal papillary mucinous neoplasm by immunohistochemistry and revealed that programmed cell death 4 expression was recognized in both the nucleus and cytoplasm in intraductal papillary mucinous neoplasm. The positive rate of programmed cell death 4 was 79%, 43%, and 10% in adenoma, borderline, and carcinoma, respectively. The positive rate of programmed cell death 4 decreased from adenoma to carcinoma (P < .0001, both adenoma versus borderline and borderline versus carcinoma), indicating that programmed cell death 4 might inhibit tumor progression in intraductal papillary mucinous neoplasm. Programmed cell death 4 expression had a strong relationship with p21 expression (P < .0001) and an inverse correlation with Ki-67 labeling index (r = -0.6255, P < .0001). Thus, programmed cell death 4 might inhibit the proliferation of intraductal papillary mucinous neoplasm; and its inhibition might partly result from cell cycle arrest caused by the up-regulation of p21. In conclusion, programmed cell death 4 may inhibit tumor progression in intraductal papillary mucinous neoplasm; and the loss of programmed cell death 4 expression is representative of the malignant potential of intraductal papillary mucinous neoplasm including the proliferative activity. Therefore, programmed cell death 4 can be an important biomarker for intraductal papillary mucinous neoplasm.
导管内乳头状黏液性肿瘤的特征是主胰管和/或分支胰管囊性扩张，伴有黏液。根据异型程度，导管内乳头状黏液性肿瘤可分为 3 组：腺瘤、交界性和癌。此外，导管内乳头状黏液性肿瘤被认为像结直肠癌一样通过腺瘤-癌序列进展。程序性细胞死亡蛋白 4 是一种最近发现的肿瘤抑制因子，被发现可抑制翻译。程序性细胞死亡蛋白 4 已被报道可抑制多种人类恶性肿瘤的肿瘤发生、肿瘤进展、增殖、侵袭和转移。我们通过免疫组织化学检查了 108 例导管内乳头状黏液性肿瘤，发现程序性细胞死亡蛋白 4 在导管内乳头状黏液性肿瘤的细胞核和细胞质中均有表达。在腺瘤、交界性和癌中，程序性细胞死亡蛋白 4 的阳性率分别为 79%、43%和 10%。程序性细胞死亡蛋白 4 的阳性率从腺瘤到癌逐渐降低（P<0.0001，均为腺瘤与交界性和交界性与癌），表明程序性细胞死亡蛋白 4 可能抑制导管内乳头状黏液性肿瘤的肿瘤进展。程序性细胞死亡蛋白 4 的表达与 p21 的表达呈强相关（P<0.0001），与 Ki-67 标记指数呈负相关（r=-0.6255，P<0.0001）。因此，程序性细胞死亡蛋白 4 可能抑制导管内乳头状黏液性肿瘤的增殖；其抑制作用可能部分归因于 p21 上调引起的细胞周期停滞。总之，程序性细胞死亡蛋白 4 可能抑制导管内乳头状黏液性肿瘤的肿瘤进展；程序性细胞死亡蛋白 4 的表达缺失代表了导管内乳头状黏液性肿瘤的恶性潜能，包括增殖活性。因此，程序性细胞死亡蛋白 4 可以成为导管内乳头状黏液性肿瘤的一个重要生物标志物。
