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

https://doi.org/10.1016/j.jaad.2012.03.007Get rights and content

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.

Section snippets

Patients

Six tertiary care hospitals of Spain participated in this study. Records at these centers were searched to identify patients who had developed MSCCs between 2001 and 2010. Fifty patients with 51 primary MSCCs that had evolved to histologically confirmed lymph node (n = 46) or cutaneous in-transit (n = 5) metastases were included in the study. A control group of 50 patients with cSCCs who had not developed any metastasis (non-MSCCs) in a 5-year follow-up period was also evaluated. All the tumors

Lymphatic metastases status and clinicopathological features

The clinicopathological features of the patients and tumors are detailed in Table I. The mean follow-up period of time in the MSCC group was 24 months. The mean period of time between the diagnosis of the primary MSCCs and their lymphatic metastases was 7.2 months (n = 44). Four of the 101 (3.9%) cSCCs in the study showed angiolymphatic invasion on basis of the hematoxylin-eosin staining.

No differences regarding gender, age, sun-exposed area, or immunosuppression status were observed between

Discussion

There is a lack of reliable prognostic markers in cSCC. It would be of special interest to identify aggressive tumors that require additional treatments such as lymphadenectomy or radiation therapy. We have evaluated the use of podoplanin expression as a prognostic marker in cSCC.

Lymphatic invasion is rarely seen in primary cSCC by routine histology probably because of obliteration and solid tumor emboli that make it imperceptible. We have shown that D2-40 positivity in endothelial cells helps

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    Supported in part by grants PI041728, PI10/00785, and RD09/0076/00036 from Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Ministerio de Sanidad, Federación Española de Enfermedades Raras (FEDER), Spain, and the Xarxa de Bancs de tumors sponsored by Pla Director d'Oncologia de Catalunya.

    Conflicts of interest: None declared.

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