Investigation of clinical application of claudin 18 isoform 2 in pancreatic ductal adenocarcinoma: A retrospective analysis of 302 chinese patients

• Zhiwen Zhang ^[1] ; Xiaoding Liu ^[1] ; Liangrui Zhou ^[1] ; Mu Zhang ^[1] ; Zhiyong Liang ^[1]
  1. [1] Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
• Localización: Histology and histopathology: cellular and molecular biology, ISSN-e 1699-5848, ISSN 0213-3911, Vol. 37, Nº. 10, 2022, págs. 1031-1040
• Idioma: inglés
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• Resumen

  • The malignancy of pancreatic ductal adenocarcinoma (PDAC) results from high frequency of recurrence and limited effective therapies. Targeted therapy is a promising treatment in multiple solid tumours. A new target, claudin 18 isoform 2 (CLDN18.2) was discovered in gastric and pancreatic adenocarcinoma, but more clinical evaluations of CLDN18.2 are still needed. Several CLDN18.2-targeted drugs have already been in procedure of clinical trials.

    Therefore, the present study aimed to explore the expression and clinical value of CLDN18.2 in PDAC by immunohistochemistry. A microarray cohort of 302 PDAC specimens and a whole-slide cohort of randomized 84 PDAC specimens were constructed. In total, 56.52% (171/302) of PDAC patients showed diverse positivity for CLDN18.2, especially in highly differentiated PDAC. About eighty-two percent (62/75) highly- and 62.61% (72/115) intermediate-differentiated PDAC showed positive for CLDN18.2, while only 10.16% (6/59) low differentiated PDAC was positive for CLDN18.2. Besides, CLDN18.2 positivity was associated with several clinicopathological characteristics, including sex (P=0.001), smoking (P=0.006), abdominal pain (P=0.021), jaundice (P=0.010), pathological differentiation (P=0.001), common bile duct invasion (P=0.010), and M stage (P=0.003). CLDN18.2-positive expression also predicts an improved survival (P=0.032) but not progression free survival (P=0.460). However, CLDN18.2 is not an independent prognostic predictor. In conclusion, CLDN18.2 may be a potential therapeutic target for PDAC and the study supplies persuasive pathological evidence for CLDN18.2-targeted therapy on PDAC patients.