We compared clinicopathologic and molecular features of esophageal squamous cell carcinoma (SCC) with basaloid features to conventional SCC using surgical resections of treatment naïve esophageal carcinomas and cases available from the TCGA database. Twenty-two cases of SCC with basaloid features were identified in the Mass General Brigham pathology archives, including 9 cases with pure basaloid morphology and 13 cases with mixed other features such as conventional well- or poorly differentiated areas or sarcomatoid areas. Thirty-eight cases of conventional SCC matched by tumor stage were used as controls. HPV infection status was tested by p16 immunohistochemistry and HPV mRNA ISH. Digital slides for 94 cases of esophageal SCC from TCGA found in the Genomic Data Commons (GDC) Data Portal were reviewed. Five cases of SCC with basaloid features were identified. Genomic profiles of SCC with basaloid features were compared to the rest of 89 SCCs without basaloid features. In addition, eight tumor sections from six patients selected from our cohort underwent in-house molecular profiling. Compared to conventional SCC, SCC with basaloid features were more frequently associated with diffuse or multifocal squamous dysplasia (p < 0.001). P16 IHC was positive in 2/13 cases, whereas HPV mRNA ISH was negative in 17/17 cases (including both p16-positive cases). SCC with basaloid features and conventional SCC from TCGA showed similar rates of TP53 mutations, CDKN2A/B deletions, and CCDN1 amplifications. TP53 variants were identified in all in-house samples that had sufficient coverage. Survival analyses between SCC with basaloid features versus conventional SCC (matched for tumor stage) did not reveal any statistically significant differences. In conclusion, esophageal SCC with basaloid features has similar survival and genomic alterations to those of conventional SCC, are more frequently associated with diffuse or multifocal dysplasia, and are not associated with HPV (high-risk strains) infection.
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The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. The publicly available datasets analyzed during the current study are available here: www.portal.gdc.cancer.gov.
SEER Cancer Statistics Review, 1975-2017. Bethesda, MD: National Cancer Institute, 2020.
Tachimori, Y. et al. Comprehensive registry of esophageal cancer in Japan, 2009. Esophagus 13, 110–137 (2016).
Maebayashi, T. et al. A long-surviving patient with advanced esophageal basaloid squamous cell carcinoma treated only with radiotherapy: case report and literature review. BMC Gastroenterol 17, 151 (2017).
Suzuki, H. & Nagayo, T. Primary tumors of the esophagus other than squamous cell carcinoma-histologic classification and statistics in the surgical and autopsied materials in Japan. Int. Adv. Surg. Oncol. 3, 73–109 (1980).
Morales-Puebla, J. M., Toro-Rojas, M., Segura-Saint-Gerons, R., Fanego-Fernández, J. & López-Villarejo, P. Basaloid squamous cell carcinoma: report of five cases. Med. Oral Patol. Oral Cir. Bucal 15, 451–455 (2010).
Wain, S. L., Kier, R., Vollmer, R. T. & Bossen, E. H. Basaloid-squamous carcinoma of the tongue, hypopharynx, and larynx: report of 10 cases. Hum Pathol 17, 1158–1166 (1986).
Sekiguchi, K. et al. Pulmonary metastasectomy for esophageal basaloid squamous cell carcinoma component at 66 months after esophagectomy. Surg. Case Rep. 6, 199 (2020).
Zhang, X. H., Sun, G. Q., Zhou, X. J., Guo, H. F. & Zhang, T. H. Basaloid squamous carcinoma of esophagus: a clinicopathological, immunohistochemical and electron microscopic study of sixteen cases. World J. Gastroenterol 4, 397–403 (1998).
Epstein, J. I., Sears, D. L., Tucker, R. S. & Eagan, J. W. Carcinoma of the esophagus with adenoid cystic differentiation. Cancer 53, 1131–1136 (1984).
Huang, Z., Liang, Y. & Wu, X. [Basaloid squamous carcinoma of the oesophagus: a distinctive clinico-pathological entity]. Chin. J. Pathol 24, 90–92 (1995).
Abe, K. et al. Basaloid-squamous carcinoma of the esophagus. A clinicopathologic, DNA ploidy, and immunohistochemical study of seven cases. Am. J. Surg. Pathol. 20, 453–461 (1996).
Board WCoTE. WHO Classification of Tumours: Digestive System Tumours. Lyon (France) 2019.
Cho, K. J., Jang, J. J., Lee, S. S. & Zo, J. I. Basaloid squamous carcinoma of the oesophagus: a distinct neoplasm with multipotential differentiation. Histopathology 36, 331–340 (2000).
Kumagai, Y. et al. Clinicopathologic characteristics and clinical outcomes of esophageal basaloid squamous carcinoma: experience at a single institution. Int. Surg. 98, 450–454 (2013).
Chen, S. B. et al. Basaloid squamous cell carcinoma of the esophagus. J. Cancer Res. Clin. Oncol. 138, 1165–1171 (2012).
Sarbia, M. et al. Basaloid squamous cell carcinoma of the esophagus: diagnosis and prognosis. Cancer 79, 1871–1878 (1997).
Lin, D. C., Wang, M. R. & Koeffler, H. P. Genomic and epigenomic aberrations in esophageal squamous cell carcinoma and implications for patients. Gastroenterology 154, 374–389 (2018).
Network, C. G. A. R. et al. Integrated genomic characterization of oesophageal carcinoma. Nature 541, 169–175 (2017).
Isidro R. A. et al. Verrucous carcinoma of the esophagus is a genetically distinct subtype of esophageal squamous cell carcinoma. Histopathology. (2021). https://doi.org/10.1111/his.14395.
Garcia, E. P. et al. Validation of OncoPanel: a targeted next-generation sequencing assay for the detection of somatic variants in cancer. Arch. Pathol Lab. Med. 141, 751–758 (2017).
Bellizzi, A. M. et al. Basaloid squamous cell carcinoma of the esophagus: assessment for high-risk human papillomavirus and related molecular markers. Am. J. Surg. Pathol. 33, 1608–1614 (2009).
Yamasaki, T. et al. A case of esophageal squamous cell carcinoma with neuroendocrine, basaloid, and ciliated glandular differentiation. Clin. J. Gastroenterol 14, 32–38 (2021).
Lam, K. Y., Ma, L. T. & Wong, J. Measurement of extent of spread of oesophageal squamous carcinoma by serial sectioning. J. Clin. Pathol. 49, 124–129 (1996).
Rahimi, S. HPV-related squamous cell carcinoma of oropharynx: a review. J. Clin. Pathol. 73, 624–629 (2020).
Rajendra, S., Pavey, D., McKay, O., Merrett, N. & Gautam, S. D. Human papillomavirus infection in esophageal squamous cell carcinoma and esophageal adenocarcinoma: a concise review. Ann. NY Acad. Sci. 1482, 36–48 (2020).
Mohammadpour, B., Rouhi, S., Khodabandehloo, M. & Moradi, M. Prevalence and association of human papillomavirus with esophageal squamous cell carcinoma in Iran: a systematic review and meta-analysis. Iran J. Public Health 48, 1215–1226 (2019).
Liu, Y., Zhao, L., Xue, L. & Hou, Y. Selected updates in molecular and genomic pathology of esophageal cancer. Ann. NY Acad. Sci. 1482, 225–235 (2020).
Singh, T. et al. Human papillomavirus infection and p53 mutation in esophageal squamous cell carcinoma and its impact on treatment outcome. J Cancer Res. Ther. 16(Supplement), S150–S155 (2020).
Emanuel, P., Wang, B., Wu, M. & Burstein, D. E. p63 Immunohistochemistry in the distinction of adenoid cystic carcinoma from basaloid squamous cell carcinoma. Mod Pathol 18, 645–650 (2005).
Salami, A., Abbas, A. E., Petrov, R., Jhala, N. & Bakhos, C. T. Comparative analysis of clinical, treatment, and survival characteristics of basaloid and squamous cell carcinoma of the esophagus. J. Am. Coll Surg. 226, 1086–1092 (2018).
Lam, K. Y., Law, S., Luk, J. M. & Wong, J. Oesophageal basaloid squamous cell carcinoma: a unique clinicopathological entity with telomerase activity as a prognostic indicator. J. Pathol. 195, 435–442 (2001).
Sato-Kuwabara, Y. et al. Comparative analysis of basaloid and conventional squamous cell carcinomas of the esophagus: prognostic relevance of clinicopathological features and protein expression. Tumour Biol. 37, 6691–6699 (2016).
We thank Ms. Diana McGraw for administrative support.
The authors received no external funding for this work. This study was supported through intradepartmental funds.
M.A.S., J.Y., R.A.I., F.D., J.O.W., A.A., D.P., and L.Z. have no relevant financial disclosures. V.D. serves on the Scientific advisory boards of Incyte and Viela and receives research support from Advanced Cell Diagnostic and Agios.
Ethics Approval/Consent to Participate
This retrospective study was approved by the Institutional Review Board of Mass General Brigham (protocol #2018P001007). No human subjects were recruited for the study.
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Sauer, M.A., Yang, J., Isidro, R.A. et al. Esophageal squamous cell carcinoma with basaloid features are genetically and prognostically similar to conventional squamous cell carcinoma. Mod Pathol (2022). https://doi.org/10.1038/s41379-022-01060-4