Evaluating CSPG4 expression in esophageal basaloid squamous cell carcinoma and conventional squamous cell carcinoma: a multi-institutional retrospective study in China.

Esophageal basaloid squamous cell carcinoma (EBSCC) is a rare subtype of esophageal squamous cell carcinoma (ESCC) that might be misdiagnosed or missed in clinical practice. Through RNA sequencing on 20 pure EBSCC and 11 poorly differentiated ESCC samples, we identified CSPG4 as a potential marker for EBSCC at the mRNA level, and verified with CSPG4 immunohistochemical staining in these cases. Then we assessed the value of CSPG4 expression in differential diagnosis and prognosis in EBSCC cases (n = 360) and conventional ESCC cases (n = 160) from 11 different institutions with whole-tissue sections. CSPG4 had acceptable discriminatory capacity for EBSCC, with an AUC ROC of 0.891. The optimal cutoff value for the H-score determined by ROC curve analysis was 77.5, with 82.7% sensitivity and 79.9% specificity. In well-moderately differentiated ESCC with CSPG4 expression, staining was mostly observed on the edge of the tumor nest or infiltration front, with different expression pattern from EBSCC. The H-scores of CSPG4 expression for the EBSCC component were higher than those for other components in the same tissue section (P < 0.05). The expression level of CSPG4 was similar in groups with different percentages of the EBSCC component (P > 0.05). In additional 505 ESCC patients, patients with high CSPG4 expression had decreased DFS and OS, especially in stage I-II disease (P < 0.001). The similar prognostic significance was also found in EBSCC. Our data indicate that CSPG4 is not only a sensitive but also a specific marker for the diagnosis of EBSCC. CSPG4 might also be a prognostic marker for ESCC.