Non-ampullary small bowel adenocarcinoma is a rare neoplasm with an ominous prognosis, whose incidence is higher in some chronic immuno-inflammatory conditions, such as coeliac and Crohn's disease. Recently, claudin 18.2, a transmembrane protein normally expressed in gastric mucosa, has been recognized as a novel pan-cancer therapeutic target, and several clinical trials with claudin-18-directed drugs have shown promising results on various gastrointestinal malignancies. This is the first study focusing on claudin-18 expression in small bowel adenocarcinomas. The immunohistochemical expression of claudin-18 (clone 43-14A) was assessed in 81 small bowel adenocarcinomas of diverse aetiologies and correlated with several clinico-pathologic features and patient survival. We found that 28% of adenocarcinomas were immunoreactive for claudin-18, with cutoff values of >= 1% at any intensity, while 6% of cancers showed immunoexpression of >= 75% with 2+/3+ score. Moreover, claudin-18 (>= 1%) was positively associated with cytokeratin 7 (CK7) and MUC5AC expression, showing CK7+/MUC5AC+ carcinomas the highest rate of positive cases, whereas a negative correlation was found between claudin-18 and CDX2 expression. In addition, some cancer-adjacent dysplastic growths and foci of gastric-type metaplasia in Crohn's disease-associated cases showed claudin-18 immunoreactivity. Survival analysis showed a non-significant trend towards a worse cancer-specific survival for claudin-18-positive cases. A fraction of small bowel adenocarcinomas, mainly sporadic or Crohn's disease-associated, and often exhibiting a non-intestinal immunoprofile, expressed claudin-18, suggesting that claudin-18-directed targeted therapy is worth investigating in such cancers.
Claudin-18 expression in small bowel adenocarcinoma: a clinico-pathologic study
Arpa, Giovanni;Guerini, Camilla;Quaquarini, Erica;Lenti, Marco Vincenzo;Pedrazzoli, Paolo;Paulli, Marco;Di Sabatino, Antonio;Vanoli, Alessandro
2022-01-01
Abstract
Non-ampullary small bowel adenocarcinoma is a rare neoplasm with an ominous prognosis, whose incidence is higher in some chronic immuno-inflammatory conditions, such as coeliac and Crohn's disease. Recently, claudin 18.2, a transmembrane protein normally expressed in gastric mucosa, has been recognized as a novel pan-cancer therapeutic target, and several clinical trials with claudin-18-directed drugs have shown promising results on various gastrointestinal malignancies. This is the first study focusing on claudin-18 expression in small bowel adenocarcinomas. The immunohistochemical expression of claudin-18 (clone 43-14A) was assessed in 81 small bowel adenocarcinomas of diverse aetiologies and correlated with several clinico-pathologic features and patient survival. We found that 28% of adenocarcinomas were immunoreactive for claudin-18, with cutoff values of >= 1% at any intensity, while 6% of cancers showed immunoexpression of >= 75% with 2+/3+ score. Moreover, claudin-18 (>= 1%) was positively associated with cytokeratin 7 (CK7) and MUC5AC expression, showing CK7+/MUC5AC+ carcinomas the highest rate of positive cases, whereas a negative correlation was found between claudin-18 and CDX2 expression. In addition, some cancer-adjacent dysplastic growths and foci of gastric-type metaplasia in Crohn's disease-associated cases showed claudin-18 immunoreactivity. Survival analysis showed a non-significant trend towards a worse cancer-specific survival for claudin-18-positive cases. A fraction of small bowel adenocarcinomas, mainly sporadic or Crohn's disease-associated, and often exhibiting a non-intestinal immunoprofile, expressed claudin-18, suggesting that claudin-18-directed targeted therapy is worth investigating in such cancers.File | Dimensione | Formato | |
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Descrizione: Arpa G, Fassan M, Guerini C, Quaquarini E, Grillo F, Angerilli V, Guzzardo V, Lonardi S, Bergamo F, Lenti MV, Pedrazzoli P, Paulli M, Di Sabatino A, Vanoli A. Claudin-18 expression in small bowel adenocarcinoma: a clinico-pathologic study. Virchows Arch. 2022 Dec;481(6):853-863. doi: 10.1007/s00428-022-03393-6. Epub 2022 Aug 4. PMID: 35925388; PMCID: PMC9734203.
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