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Introduction Heparan sulfate proteoglycans (HSPGs) belong to the syndecan family, and syndecan-1 (CD138) is a heparan sulfate proteoglycan. Syndecan-1 has a potential role in cell-matrix and cell-cell communications as they are present in cell epithelium. Its expression is different in an extensive range of benign, inflammatory, and neoplastic diseases. In routine histopathology, it is used as a marker for plasma cells. However, it is expressed in a large variety of normal and neoplastic epithelia including squamous epithelium and gastric glandular epithelium expressed in other tissues, i.e., the liver. In the liver, variable expression is seen in cirrhosis, hepatitis, and carcinoma. The objective of this study was to investigate the expression of this marker in normal, inflammatory, and neoplastic lesions of the liver. This in turn may help clinicians to select patients who may benefit from anti-CD138 therapy. It is currently used in the diagnosis and management of plasma cell proliferations. Material and methods This is a retrospective study in which we retrieved 53 formalin-fixed paraffin-embedded (FFPE) liver specimen blocks and selected one block from each case by reviewing the hematoxylin and eosin (H&E) slides of each case. Syndecan-1 (CD138), pancytokeratin, and CD68 expression were analyzed immunohistochemically (IHC) to evaluate the percentage and intensity of CD138 expression in various hepatic entities and identify those entities where syndecan-1 can be consistently used to make a definitive diagnosis. Results The expression of pancytokeratin and CD68 was analyzed in hepatocytes and Kupffer cells, respectively. For syndecan-1 (CD138), 15.4% of cases showed basolateral membranous positivity, 44.6% of cases showed complete membranous positivity, and 40% of cases showed no positivity in hepatocytes. Cytokeratin (CK) was positive as expected in hepatocytes, and CD68 was expressed in Kupffer cells. Conclusion CD138 does not appear to be a reliable surrogate marker for liver disease. However, it may be included with other ancillary markers as a predictor of the stage of chronic liver disease and metastatic potential. The response to anti-CD138 therapy needs to be further studied.
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BACKGROUND: Recent evidence from randomized trials suggests that FOLFOXIRI (fluorouracil, oxaliplatin, and irinotecan) ± bevacizumab is associated with higher response rates, with the potential for conversion of unresectable to resectable disease in metastatic colorectal cancer (mCRC). However, limited evidence is available on the efficacy and safety of this regimen in real-world patients with mCRC. The current study aims to evaluate the conversion rate and safety of FOLFOXIRI ± bevacizumab in real-world patients with unresectable mCRC. METHODS: In this retrospective multicenter population-based cohort study, patients who were diagnosed with unresectable mCRC between January 2015 and December 2018 in Saskatchewan and received FOLFOXIRI ± bevacizumab were assessed. Kaplan-Meier survival methods and the log-rank test were performed. RESULTS: A total of 28 eligible patients with a median age of 51 years (interquartile range 39-60) and a male:female ratio of 11:17 were identified; 39% had rectal cancer, 46% had extrahepatic disease, and 46% had bilobar liver metastases. Overall, 63% of the patients had a positive response to FOLFOXIRI ± bevacizumab and 53% underwent metastasectomy. Of all patients 60% had grade 3/4 toxicity and 32% required hospital admission. No treatment-related mortality was noted. After 4 years, 50% of the patients were alive. Median progression-free survival of patients who underwent surgery was 18 months (95% CI 11.3-24.7) versus 11 months (4-18.1) without surgery (p = 0.28). Median overall survival of patients with surgery was 33 months (17.5-48.5) versus 16 months (8.3-23.7) without surgery (p = 0.03). CONCLUSION: The current study suggests that FOLFOXIRI ± bevacizumab therapy in real-world patients with mCRC is associated with a high rate of conversion from unresectable to resectable metastatic disease. Patients with metastasectomy had better survival.
