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

Ups J Med Sci. 2020 Feb;125(1):19-29. doi: 10.1080/03009734.2019.1692101. Epub 2019 Dec 6.

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.

MeSH terms

  • Adenocarcinoma / diagnosis*
  • Adenocarcinoma / metabolism
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Squamous Cell / diagnosis*
  • Carcinoma, Squamous Cell / metabolism
  • Desmoglein 3 / metabolism
  • Desmosomes / metabolism*
  • Diagnosis, Differential
  • Female
  • Humans
  • Immunohistochemistry
  • Keratin-15 / metabolism
  • Lung Neoplasms / diagnosis*
  • Lung Neoplasms / metabolism
  • Male
  • Middle Aged
  • Plakophilins / metabolism
  • Prognosis
  • Sensitivity and Specificity

Substances

  • Biomarkers, Tumor
  • DSG3 protein, human
  • Desmoglein 3
  • KRT15 protein, human
  • Keratin-15
  • PKP1 protein, human
  • Plakophilins

Grants and 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).