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. 2017 May 9;8(19):31532-31539.
doi: 10.18632/oncotarget.16360.

Gallbladder papillary neoplasms share pathological features with intraductal papillary neoplasm of the bile duct

Xueshuai Wan  1 , Jie Shi  2 , Anqiang Wang  1 , Yuan Xie  1 , Xiaobo Yang  1 , Chengpei Zhu  1 , Haohai Zhang  1 , Liangcai Wu  1 , Shanshan Wang  1 , Hanchun Huang  1 , Jianzhen Lin  1 , Yongchang Zheng  1 , Zhiyong Liang  2 , Xinting Sang  1 , Haitao Zhao  1
Affiliations

Gallbladder papillary neoplasms share pathological features with intraductal papillary neoplasm of the bile duct

Xueshuai Wan et al. Oncotarget. .

Abstract

Intraductal papillary neoplasm of the bile duct (IPNB) has been widely recognized. However, the knowledge of intracystic papillary neoplasm of the gallbladder (IPNG) including papillary adenoma and adenocarcinoma is not well defined. In this study, we compared the clinicopathological and immunohistochemical features between 32 IPNG cases and 32 IPNB cases. IPNG-1 (low-high grade dysplasia) exhibited an earlier onset age, smaller tumor size and lower level of CK20 expression compared to IPNG-2 (invasive carcinoma). Histologically, pancreaticobiliary and intestinal subtype accounted for nearly half of IPNG or IPNB (44.4% and 48.1% vs. 44.0% and 44.0%), respectively. Immunohistochemically, 88.9% of IPNG and 92.0% of IPNB cases were positive for MUC1, and 96.3% and 92.0% for CK7, respectively. CDX2 and MUC2 were more highly expressed in the intestinal subtype than in other subtypes. CK20 expression increased in parallel with tumor progression. In addition, 53.1% of IPNG cases and 68.6% of IPNB cases exhibited invasive carcinoma, and showed significant survival advantages to conventional gallbladder adenocarcinoma and cholangiocarcinoma, respectively. In conclusion, papillary adenoma and adenocarcinoma of the gallbladder can be recognized as different pathological stages of IPNG, and they share pathological features with IPNB.

Keywords: CDX2; cytokeratin; gallbladder; mucin; papillary.

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Conflict of interest statement

CONFLICTS OF INTEREST

There was no conflicts of interests to declare.

Figures

Figure 1
Figure 1. Histological subtypes identified in IPNG and IPNB
(A) pancreaticobiliary; (B) intestinal; (C) oncocytic; (D) gastric. H&E staining 100×.
Figure 2
Figure 2. Expression of immunohistochemical markers in tumor cells
MUC1 in the apical membrane (A) and cytoplasm of tumor cells (B) MUC2 (C) CK7 (D) and CK20 (E) in the cytoplasm; CDX2 in the nucleus (F). Immunohistochemical staining 200×.
Figure 3
Figure 3. Expression profile of immunohistochemical markers in IPNG and IPNB
MUC1 (A) and CK7 (D) were diffusely expressed in most cases of IPNG and IPNB. CK20 (B) was more frequently expressed in IPNG-2 and IPNB-2 than IPNG-1 and IPNB-1, respectively. IPNB-2 expressed more CDX2 (C) than IPNB-1. Meanwhile, the expression of CDX2 was positively correlated with CK20 expression in IPNG (E) and IPNB (F). * means P < 0.05.
Figure 4
Figure 4. The correlation among different histological subtypes and immunohistochemical markers in IPNG and IPNB
Cases with intestinal subtype expressed more MUC2 and CDX2 in IPNG (A, B) and IPNB (D, E). The expression of CDX2 was positively correlated with MUC2 expression in IPNG (C) and IPNB (F).
Figure 5
Figure 5. Survival analysis of IPNG and IPNB
The overall survival of IPNB-2 (A) and IPNG-2 (B) were significantly better than that of cholangiocarcinoma and gallbladder adenocarcinoma, respectively. There was no significant difference in overall survival between IPNB and IPNG (C). Multivariate analysis suggested that positive surgical margin (D) and lymph node involvement (E) were independent risk factors of IPNG. However, the independent risk factor of IPNB was invasive carcinoma (F).
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