D2-40 immunohistochemical overexpression in cutaneous squamous cell carcinomas: a marker of metastatic risk

J Am Acad Dermatol. 2012 Dec;67(6):1310-8. doi: 10.1016/j.jaad.2012.03.007. Epub 2012 Apr 20.

Abstract

Background: Approximately 4% of cutaneous squamous cell carcinomas (cSCCs) develop lymphatic metastases. The value of lymphatic endothelial markers to enhance the detection of lymphatic tumor invasion in cSCC has not been assessed previously.

Objective: We sought to evaluate the use of the antibody D2-40, a podoplanin immunohistochemical marker, to identify tumor lymph vessel invasion in cSCC and to assess its expression in tumor cells.

Methods: This was a retrospective case-control study. A series of 101 cSCC, including 51 cases that developed lymphatic metastatic spread (metastasizing cSCC [MSCC]) and 50 cases that resolved definitely after surgical excision (non-MSCC) were included in the study. Lymph vessel invasion using D2-40 was evaluated on all primary biopsy specimens. The percentage of tumor cells showing D2-40 positivity and intensity scoring were recorded. All the immunohistochemical findings were correlated with the clinicopathological features.

Results: Lymph vessel invasion was observed in 8% of non-MSCCs and in 25.5% of MSCCs (P = .031). D2-40 expression was significantly increased, both in intensity (odds ratio 4.42 for intensity ++/+++) and in area (odds ratio 2.29 for area >10%), in MSCC when compared with non-MSCC. Interestingly, almost half (49%) of the MSCC had moderate to intense D2-40 positivity compared with 16% of non-MSCC. D2-40 immunohistochemical expression was increased in tumors with an infiltrative pattern of extension. In the multivariate analysis, histologically poorly differentiated tumors, recurrent lesions, and cSCC showing D2-40 overexpression (in intensity) were significantly associated with lymphatic metastases development (odds ratios 15.67, 14.72, and 6.07, respectively).

Limitations: This was a retrospective study.

Conclusion: The expression of podoplanin associates with high metastatic risk in cSCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibodies, Monoclonal, Murine-Derived / analysis
  • Antibodies, Monoclonal, Murine-Derived / biosynthesis*
  • Biomarkers / analysis
  • Carcinoma, Squamous Cell / chemistry
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / secondary*
  • Case-Control Studies
  • Female
  • Humans
  • Immunohistochemistry
  • Lymphatic Metastasis
  • Male
  • Retrospective Studies
  • Risk Assessment
  • Skin Neoplasms / chemistry
  • Skin Neoplasms / metabolism*
  • Skin Neoplasms / pathology*

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Biomarkers
  • monoclonal antibody D2-40