Li Daiqiang, Yang Zhulin, Liu Ziru, Zou Qiong, Yuan Yuan
Departments of Pathology.
General Surgery, The Second Xiangya Hospital.
Appl Immunohistochem Mol Morphol. 2020 Feb;28(2):103-110. doi: 10.1097/PAI.0000000000000705.
Gallbladder cancer (GBC) is a rare disease with high mortality. However, no biomarkers for the carcinogenesis, progression, prognosis, and early diagnosis are clinically available. This study investigated the expressions of cystathionine-β-synthase (CBS) and C-C chemokine receptor 7 (CCR7) protein and their clinical and pathologic significances in gallbladder squamous cell/adenosquamous carcinomas (SC/ASC) and adenocarcinomas (AC). CBS and chemokine ligand 21 (CCL21) expression was measured using immunohistochemistry in 69 SC/ASCs and 146 ACs. A significantly high percentage of patients with an age above 45 years, lymph node metastasis, and invasion was observed in the SCs/ASCs compared with ACs (P<0.05). Both AC and SC/ASC patients with positive CBS and CCL21 expression exhibited a high tumor-lymph node-metastasis stage, lymph node metastasis, and invasion compared with patients with negative CBS and CCL21 expression (P<0.05 or P<0.01). SC/ASC patients with positive CBS expression was prone to have a larger tumor size than those with negative expression (P<0.05). Positive CBS and CCL21 expression correlated with poor differentiation and larger tumor size in AC patients. Positive CBS and CCL21 are closely associated with a decreased overall survival in SC/ASC and AC patients (P<0.05 or P<0.01) and were independent factors for a poor-prognosis. Both CBS and CCL21 showed a good overall diagnostic performance for SC/ASC (AUC=0.742 and AUC=0.764, respectively) and AC (AUC=0.734 and AUC=0.718, respectively). In conclusion, positive CBS and CCL21 expression are closely associated with the clinical severity and poor prognosis in GBC, and can be a marker for the diagnosis of AC and SC/ASC type of GBC.
胆囊癌（GBC）是一种死亡率很高的罕见疾病。然而，临床上尚无用于致癌、进展、预后及早期诊断的生物标志物。本研究调查了胱硫醚-β-合酶（CBS）和C-C趋化因子受体7（CCR7）蛋白在胆囊鳞状细胞/腺鳞癌（SC/ASC）和腺癌（AC）中的表达及其临床和病理意义。采用免疫组织化学法检测69例SC/ASC和146例AC中CBS和趋化因子配体21（CCL21）的表达。与AC患者相比，SCs/ASCs中年龄大于45岁、有淋巴结转移和浸润的患者比例显著更高（P<0.05）。与CBS和CCL21表达阴性的患者相比，CBS和CCL21表达阳性的AC和SC/ASC患者均表现出高肿瘤-淋巴结-转移分期、淋巴结转移和浸润（P<0.05或P<0.01）。CBS表达阳性的SC/ASC患者的肿瘤大小往往比阴性表达者更大（P<0.05）。AC患者中CBS和CCL21表达阳性与低分化和更大的肿瘤大小相关。CBS和CCL21表达阳性与SC/ASC和AC患者的总生存期降低密切相关（P<0.05或P<0.01），并且是预后不良的独立因素。CBS和CCL21对SC/ASC（AUC分别为0.742和0.764）和AC（AUC分别为0.734和0.718）均显示出良好的总体诊断性能。总之，CBS和CCL21表达阳性与GBC的临床严重程度和不良预后密切相关，并且可作为诊断AC和SC/ASC型GBC的标志物。
