SOX6 is a Novel Immunohistochemical Marker for Differential Diagnosis of Epithelioid Mesothelioma From Lung Adenocarcinoma

Abstract

The differential diagnosis of epithelioid mesothelioma from lung adenocarcinoma using immunohistochemistry is improving. However, immunohistochemical markers with high sensitivity and specificity have yet to be identified. In this study, we investigated the utility of sex-determining region Y box 6 (SOX6) as a novel immunohistochemical marker, identified by analyzing previous gene expression data. Immunohistochemically, SOX6 expression was present in 53 of 54 (98%) cases of epithelioid mesothelioma, compared with its expression in only 5 of 69 (7%) cases of lung adenocarcinoma. The sensitivity and specificity of SOX6 expression for differentiating epithelioid mesothelioma and lung adenocarcinoma were 98% and 93%, respectively. SOX6 expression showed similar sensitivity and far better specificity than those of calretinin or podoplanin (D2-40). In addition, SOX6 expression was more sensitive than Wilms’ tumor 1 expression. The combination of SOX6 with other markers showed comparable or better sensitivity and specificity relative to other combinations. In particular, the sensitivity of positivity for both SOX6 and calretinin (96%) and the specificity of positivity for both SOX6 and Wilms’ tumor 1 (93%) were higher than those of the other combinations. In conclusion, SOX6 is a novel candidate immunohistochemical marker for differentiating epithelioid mesothelioma from lung adenocarcinoma.

SOX6 Expression Is Sensitive for Peritoneal Epithelioid Malignant Mesothelioma, But Not Specific in the Differential Diagnosis With Tubo-ovarian Serous Neoplasia

“…SOX6 is a newly described immunohistochemical biomarker of mesothelial differentiation and is reportedly highly sensitive and specific for pleural mesothelioma when lung adenocarcinoma is in the differential diagnosis. 13 In this study, we characterized SOX6 expression in peritoneal mesothelial lesions and tuboovarian serous tumors, with 2 principal conclusions:…”

“…These findings are also in keeping with a prior report on SOX6 expression in pleural MM, in which the authors found SOX6 expression in an ovarian carcinoma metastatic to the lung. 13 Published data on SOX6 expression in tubo-ovarian serous tumors are limited. One study of 26 ovarian HGSC and endometrioid carcinoma found that SOX6 protein was significantly less abundant in tumor tissue than in non-neoplastic ovarian tissue.…”

“…Overall, 42 (98%) of 43 epithelioid MM expressed SOX6 (median SOX6 extent, 100%; mean, 82%; range, 0% to 100%). Using the 10% cutoff proposed by Kambara et al, 13 41/43 (95%) were classified as positive for SOX6, with 24 (56%) showing diffuse ( ≥ 95%) and 17 (40%) showing nondiffuse (10% to 94%) SOX6 expression. Of 2 epithelioid MM classified as negative for SOX6, 1 expressed SOX6 in 5% of cells, and 1 showed no SOX6 staining.…”

Identification of a novel circ_0001946/miR‐1290/SOX6 ceRNA network in esophageal squamous cell cancer

“…[23][24][25][26] SRY-box transcription factor 6 (SOX6), a HMG-box transcription factor, is underexpressed in the majority of human cancers, such as Ewing sarcoma, leukemia, and lung adenocarcinoma. [27][28][29] Functional studies in ESCC cell lines indicate that SOX6 has anticancer activity in ESCC. [30][31][32][33] Here, our findings support the suppressive activity of circ_0001946 in ESCC cell malignant phenotypes.…”

“…SRY‐box transcription factor 6 (SOX6), a HMG‐box transcription factor, is underexpressed in the majority of human cancers, such as Ewing sarcoma, leukemia, and lung adenocarcinoma 27–29 . Functional studies in ESCC cell lines indicate that SOX6 has anticancer activity in ESCC 30–33 .…”