The value of desmosomal plaque-related markers to distinguish squamous cell carcinoma and adenocarcinoma of the lung

Abstract

Background: An antibody panel is needed to definitively differentiate between adenocarcinoma (AC) and squamous cell carcinoma (SCC) in order to meet more stringent requirements for the histologic classification of lung cancers. Staining of desmosomal plaque-related proteins may be useful in the diagnosis of lung SCC.

Materials and methods: We compared the usefulness of six conventional (CK5/6, p40, p63, CK7, TTF1, and Napsin A) and three novel (PKP1, KRT15, and DSG3) markers to distinguish between lung SCC and AC in 85 small biopsy specimens (41 ACs and 44 SCCs). Correlations were examined between expression of the markers and patients’ histologic and clinical data.

Results: The specificity for SCC of membrane staining for PKP1, KRT15, and DSG3 was 97.4%, 94.6%, and 100%, respectively, and it was 100% when the markers were used together and in combination with the conventional markers (AUCs of 0.7619 for Panel 1 SCC, 0.7375 for Panel 2 SCC, 0.8552 for Panel 1 AC, and 0.8088 for Panel 2 AC). In a stepwise multivariate logistic regression model, the combination of CK5/6, p63, and PKP1 in membrane was the optimal panel to differentiate between SCC and AC, with a percentage correct classification of 96.2% overall (94.6% of ACs and 97.6% of SCCs). PKP1 and DSG3 are related to the prognosis.

Conclusions: PKP1, KRT15, and DSG3 are highly specific for SCC, but they were more useful to differentiate between SCC and AC when used together and in combination with conventional markers. PKP1 and DSG3 expressions may have prognostic value.

Keywords:

• Adenocarcinoma
• desmosomal plaque proteins
• non-small-cell lung cancer
• squamous cell carcinoma

Author contributions

IG, MGM, IDC, AA, and MCM performed and validated experiments. MTML and JMP analyzed the data. MEFV and MGM wrote the paper, reviewed and edited the manuscript, and provided conceptualization, validation, supervision, expertise, and feedback. MEFV participated in the funding acquisition and project administration.

Disclosure statement

The authors report no conflicts of interest.

Additional information

Funding

MEFV was supported by PAIDI programme, Group BIO309, Junta de Andalucía. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. JMP was supported by fellowships from Fundación Anticancer San Francisco Javier y Santa Cándida and Granada University contracts (law 14/2011 programme 6B).

Notes on contributors

Inmaculada Galindo

Inmaculada Galindo is an MD and PhD Student of the program in Biochemistry and Molecular Biology of University of Granada. This study forms part of the doctoral thesis of Inmaculada Galindo.

Mercedes Gómez-Morales

Mercedes Gómez-Morales is a Senior Specialist in Pathology at Department of Pathology of School of Medicine, University of Granada, Granada, Spain.

Inés Díaz-Cano

Inés Díaz-Cano is a researcher from Sistema Nacional de Garantía Juvenil y del Programa Operativo de Empleo Juvenil at Department of Biochemistry and Molecular Biology III, School of Medicine, University of Granada, Centre for Genomics and Oncological Research (GENYO) and Institute for Biomedical Research (IBS. Granada), University Hospital Complex of Granada/University of Granada, Granada, Spain.

Álvaro Andrades

Álvaro Andrades is a PhD student at Centre for Genomics and Oncological Research (GENYO) and Department of Biochemistry and Molecular Biology I, University of Granada, Granada, Spain.

Mercedes Caba-Molina

Mercedes Caba-Molina is a Senior Specialist in Pathology at Department of Pathology of School of Medicine, University of Granada, Granada, Spain.

María Teresa Miranda-León

María Teresa Miranda-León is a Senior Specialist at Department of Statistics and Operative Research, School of Medicine, University of Granada, Spain.

Pedro Pablo Medina

Pedro Pablo Medina at Centre for Genomics and Oncological Research (GENYO) and Department of Biochemistry and Molecular Biology I, University of Granada, Granada, Spain.

Joel Martín-Padron

Joel Martín-Padrón is a PhD student supported by fellowship from Fundación Anticáncer San Francisco Javier y Santa Cándida/UGR at Department of Biochemistry and Molecular Biology III, School of Medicine, University of Granada, Centre for Genomics and Oncological Research (GENYO) and Institute for Biomedical Research (IBS. Granada), University Hospital Complex of Granada/University of Granada, Granada, Spain.

María Esther Fárez-Vidal

María Esther Fárez-Vidal is a senior researcher at Department of Biochemistry and Molecular Biology III, School of Medicine, University of Granada and Institute for Biomedical Research (IBS. Granada), University Hospital Complex of Granada/University of Granada, Granada, Spain.