Abstract
B7-H3 is an immunomodulatory member of the B7-superfamily with limited expression in normal tissues, but overexpression in several types of cancer. Therefore it is currently being explored as a potential target for cancer immunotherapy. The biological relevance of B7-H3 expression in pancreatic cancer is unclear, while there are no data on B7-H3 expression in ampullary cancer. We aimed to compare intra-tumoral B7-H3 expression between these two closely related cancer types and analyze its association with post-surgical disease course. B7-H3 expression levels were determined by immunohistochemistry in tissue microarrays of resected tumors of 137 pancreatic cancer patients and 83 patients with ampullary cancer of the pancreato-biliary subtype. B7-H3 was more frequently expressed in cancer cells of ampullary cancer patients compared to pancreatic cancer patients (51% versus 21%; p< 0.001). In ampullary cancer patients, but not in pancreatic cancer patients, B7-H3 cancer cell expression was associated with longer disease-free survival and patient survival. However, the prognostic value of B7-H3 was lost upon adjustment for CA19-9 levels. The frequencies of B7-H3 expression in tumor stroma did not differ between the two types of cancer (66% versus 63%). In both cancer types, stromal B7-H3 expression was not associated with post-surgical disease course. Compared to pancreatic cancer, B7-H3 is more frequently expressed in cancer cells of patients with the pancreato-biliary subtype of ampullary cancer. These data suggest that B7-H3 may represent an interesting potential target for immunotherapy in ampullary cancer rather than in pancreatic cancer.
Highlights
Pancreatic carcinoma is a highly fatal form of cancer [1]
In agreement with previous studies [24, 31, 36,37,38, 40, 41], B7H3 expression in cancer cells of pancreatic and ampullary cancer patients was predominantly visible in the cytoplasm
A minority of pancreatic cancers have weak to intermediate B7-H3 expression in cancer cells, whereas a majority show weak to intermediate expression of B7-H3 in tumoral stroma
Summary
Pancreatic carcinoma is a highly fatal form of cancer [1]. Due to its asymptomatic early stage, 80 to 85% of patients present with late, non-resectable disease and have a dismal prognosis [2]. While newer chemotherapeutic treatments have somewhat improved the median survival of patients with pancreatic adenocarcinoma, both in the locally advanced [3], and metastatic setting [4, 5], overall prognosis remains. Patients who are eligible for surgical resection have a longer, but still limited, life expectancy compared to other cancers, with a 5-year survival rate of 39% (https://www.cancer.org/research/cancer-factsstatistics.html) and that is despite improvements in modern adjuvant chemotherapeutic treatments for early pancreatic cancer [6]. Two different histological subtypes of ampullary adenocarcinomas, intestinal and pancreato-biliary, are distinguished based on their epithelium of origin [9]. The pancreato-biliary subtype often grows into the pancreas, is histologically similar to pancreatic cancer, and has the worst prognosis (5 year survival rate of 20%) [10, 11]. There is an urgent need for more effective treatment strategies for both types of cancer
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