Mochidome Naoki, Koga Yutaka, Ohishi Yoshihiro, Miyazaki Tetsuyuki, Matsuda Ryota, Yamada Yuichi, Aishima Shinichi, Nakamura Masafumi, Oda Yoshinao
Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan; Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
Hum Pathol. 2021 Aug;114:44-53. doi: 10.1016/j.humpath.2021.05.001. Epub 2021 May 11.
Invasive gallbladder carcinoma (GBC) is preceded by two main types of precursor lesions: intracholecystic papillary-tubular neoplasms (ICPNs) and biliary intraepithelial neoplasias (BilINs). Invasive GBCs with an ICPN component have more favorable prognoses than those without an ICPN component. Some BilINs show a relatively exophytic papillary pattern but do not meet the ICPN criteria; at our institution, we call these papillary neoplasias. To clarify the clinical significance of papillary neoplasia, we herein examined 80 invasive GBCs and classified them into three groups based on the type of preinvasive lesions: those with ICPN (ICPN group, n = 35), those with papillary neoplasia (pap-neoplasia group, n = 13), and those without ICPN/papillary neoplasia (group without ICPN/pap-neoplasia, n = 32). We then compared the prognostic differences and characterized the tumors of each group by determining the immunohistochemical expressions of various biomarkers. The overall survival periods of the ICPN and pap-neoplasia groups were significantly longer than that of the group without ICPN/pap-neoplasia (P < 0.0001, P = 0.0036, respectively). Multivariate analysis revealed that lacking ICPN/papillary neoplasia was independently associated with poor prognosis (P = 0.0007), as were poor differentiation (P = 0.0395), presence of preoperative symptoms (P = 0.0488), and advanced stage (P = 0.0234). Invasive components of the ICPN and pap-neoplasia groups were characterized by higher expressions of p16 and p53 compared with those of the group without ICPN/pap-neoplasia. The prognoses of the invasive GBCs with either papillary neoplasia or ICPN were thus more favorable than those of the invasive GBCs without ICPN/pap-neoplasia. Invasive GBCs with exophytic papillary preinvasive lesions (ICPN and papillary neoplasia) may be biologically different from those without such lesions.
浸润性胆囊癌（GBC）之前有两种主要类型的前驱病变：胆囊内乳头管状肿瘤（ICPNs）和胆管上皮内瘤变（BilINs）。具有ICPN成分的浸润性GBC的预后比没有ICPN成分的GBC更有利。一些BilINs表现出相对外生性的乳头模式，但不符合ICPN标准；在我们机构，我们将这些称为乳头瘤变。为了阐明乳头瘤变的临床意义，我们在此检查了80例浸润性GBC，并根据浸润前病变的类型将它们分为三组：具有ICPN的（ICPN组，n = 35）、具有乳头瘤变的（乳头瘤变组，n = 13）和没有ICPN/乳头瘤变的（无ICPN/乳头瘤变组，n = 32）。然后，我们比较了预后差异，并通过确定各种生物标志物的免疫组化表达来对每组肿瘤进行特征分析。ICPN组和乳头瘤变组的总生存期明显长于无ICPN/乳头瘤变组（分别为P < 0.0001，P = 0.0036）。多因素分析显示，缺乏ICPN/乳头瘤变与预后不良独立相关（P = 0.0007），低分化（P = 0.0395）、术前有症状（P = 0.0488）和晚期（P = 0.0234）也与预后不良相关。与无ICPN/乳头瘤变组相比，ICPN组和乳头瘤变组的浸润成分特征为p16和p53表达较高。因此，具有乳头瘤变或ICPN的浸润性GBC的预后比没有ICPN/乳头瘤变的浸润性GBC更有利。具有外生性乳头浸润前病变（ICPN和乳头瘤变）的浸润性GBC在生物学上可能与没有此类病变的GBC不同。
