Pattern and Clinical Significance of CA19-9 Expression in Human Cancer: A Tissue Microarray Study on 14,966 Tumors

Carbohydrate antigen 19-9 (CA19-9) is a cell surface glycoprotein widely used as a diagnostic and prognostic serum marker for monitoring pancreatic cancer. The aim of this study was to evaluate the prevalence and clinical relevance of CA19-9 expression in human cancer.

To comprehensively determine the prevalence and clinical relevance of CA19-9 expression in cancer, a tissue microarray containing 14,966 samples from 134 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry.

The staining results were categorized into four groups according to the percentage of CA19-9-positive tumor cells and the staining intensity. At least an occasional CA19-9 positivity was found in 79 of 134 tumor categories with 66 containing at least one strongly positive case. CA19-9 positivity was most frequent in biliopancreatic adenocarcinomas (84.4%-95.4%), adenocarcinomas of the upper and lower gastrointestinal tract (54.7%-74.4%), embryonal carcinomas of the testis (93.5%), and endometrioid endometrial carcinomas (87.5%). High CA19-9 staining was associated with advanced pT-stage, pN1, L1 (p < 0.0001 each), V1 (p = 0.0239), mismatch repair protein deficiency (p = 0.0067), and BRAF V600E mutation (p = 0.0005) in colorectal adenocarcinoma. Reduced CA19-9 staining was associated with distant metastasis (p = 0.0067) in clear cell renal cell carcinoma, advanced pT-stage (p = 0.0277) in papillary renal cell carcinoma, high grade (p = 0.0129) in breast cancer and with invasive tumor growth (pTa vs. pT2-4, p < 0.0001) and high grade (p = 0.0367) in urothelial carcinoma.

It is concluded that a high CA19-9 expression, as found in pancreatic adenocarcinoma, occurs in subsets of various other cancer types. Patients with such tumors could potentially benefit from CA19-9 serum monitoring, for example in terms of response to treatment, recurrence or predicting prognosis. Cancer type dependent associations between high or low CA19-9 expression and aggressive tumor phenotype are in line with the complex and variable functional role described for CA19-9 in cancer.