Prognostic Potential of the Expression of Podoplanin (D2-40) Within Cells of Squamous Cell Carcinoma of the Larynx and Hypopharynx

Our plain-English summary of Prognostic Potential of the Expression of Podoplanin (D2-40) Within Cells of Squamous Cell Carcinoma of the Larynx and Hypopharynx, by H.U. Voelker, I. Hintermeier, A. Strehl, et al (World Journal of Oncology, 2020).

The study

• Authors: H.U. Voelker, I. Hintermeier, A. Strehl, M. Scheich
• Journal: World Journal of Oncology
• Published: 2020;11(2):65-71
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Podoplanin (D2-20) stains immunohistochemically lymphatic vessels, regular mesothelium and tumor cells of different tumors, e.g. malignant mesothelioma or seminoma. In squamous cell carcinoma (SCC), the marker has been described as variously expressed.

Methods: This study has investigated the value of the immunohistochemical analysis for the prognostic relevance of the expression in 119 SCCs of the larynx and hypopharynx. The clinical data and documentation of follow-up for at least 5 years were available.

Results: The collective showed the expected distribution of patient age with accentuation of the male sex and a balanced spread of tumor stages including nodal status. The immunohistochemical stain intensity (negative, weak or strong) and the distribution (equal versus focal) were evaluated. In addition, the accentuation of the staining reaction was separately examined at the border of invasion. SCCs with a strong expression of podoplanin were associated with an unfavorable prognosis. A comparison of grouped cases showed a trend emerging with borderline results (negative to weakly positive, P = 0.51; negative to strongly positive, P = 0.054; weakly positive to strongly positive, P = 0.17). The staining at the border of invasion had no statistical effect on overall survival. Multivariate survival statistics however showed that lymphonodal metastasis and a reaction with podoplanin in tumor cells are associated with significant worse prognosis.

Conclusion: In summary, regardless of the exact function of podoplanin in the process of cell migration and tumor progression, an immunohistochemical identification of expression in tumor cells of SCC of the larynx and hypopharynx can give additional information about the expectable prognosis.

Copyright 2020, Voelker et al.

In plain English

This article does not study asbestos exposure. It mentions malignant mesothelioma only as one of several tumors known to stain for the protein podoplanin. The authors, working at hospitals in Schweinfurt and Wuerzburg, Germany, looked back at archived tumor samples from 119 patients with squamous cell carcinoma of the larynx (70 cases) or hypopharynx (49 cases), all with at least 5 years of follow-up. They stained the tumors for podoplanin using the antibody D2-40 and compared the staining with overall survival. Staining was not linked to patient age, tumor size, stage, grade or spread to lymph nodes. Tumors with strong staining were associated with poorer survival. However, the comparisons between negative, weak and strong staining were not statistically significant: P = 0.054 for negative versus strong. In a multivariate analysis, lymph node metastasis and podoplanin staining in tumor cells were each associated with a worse prognosis. Staining at the tumor's invasion border had no independent effect on survival. The authors concluded that podoplanin staining can give additional information about expected prognosis. They said a larger group of patients could help clarify the role of staining strength.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective analysis of archived tumor samples (immunohistochemistry study with survival analysis)
• Who was studied: 119 archived cases of squamous cell carcinoma: 70 of the larynx and 49 of the hypopharynx, each with clinical data and at least 5 years of follow-up. Patients were treated by laryngectomy with neck dissection, except laryngeal pT1 tumors, which were treated by local surgery. The authors are from Schweinfurt and Wuerzburg, Germany. The years of treatment are not stated.
• Exposure: No asbestos or other occupational exposure was studied. The factor examined was immunohistochemical staining of tumor cells for podoplanin (antibody clone D2-40). Staining was graded by intensity (negative, weak or strong), by distribution (equal versus focal), and by staining at the border of invasion.
• Main results:
  • In all 119 tumors, podoplanin (D2-40) staining in tumor cells showed no correlation with patient age, tumor size, stage or grading. No statistically measurable connection with lymph node metastasis was found.
  • Significantly more laryngeal carcinomas than hypopharyngeal carcinomas were positive for D2-40 in tumor cells (P = 0.0047). Table 3 gives 63 positive laryngeal cases (91.3%) and 35 positive hypopharyngeal cases (71.4%).
  • Tumors with strong D2-40 expression (n = 69) were associated with an unfavorable prognosis. Log-rank comparisons of overall survival between the negative (n = 21), weak (n = 29) and strong groups were not significant: negative to weakly positive P = 0.51; negative to strongly positive P = 0.054; weakly positive to strongly positive P = 0.17.
  • By distribution of staining, the log-rank P values for overall survival were 0.38 for all negative versus all positive tumors, 0.12 for all positive versus focally positive tumors, and 0.031 for all negative versus focally positive tumors.
  • Staining at the border of invasion had no statistically independent effect on overall survival.
  • In the multivariate survival analysis of 119 cases, lymph node metastasis (pN+) had a hazard ratio of 2.265 (68% CI 1.712 to 2.996, P = 0.0035). A positive D2-40 reaction in tumor cells had a hazard ratio of 1.559 (68% CI 1.290 to 1.884, P = 0.019). The article reports 68% confidence intervals.
• The authors' conclusion: The authors concluded that, regardless of the exact function of podoplanin, a simple and inexpensive immunohistochemical identification of D2-40 expression in tumor cells of squamous cell carcinoma of the larynx and hypopharynx can give additional information about expected prognosis.
• Limitations the authors state:
  • The trend toward shorter survival with stronger expression was not established, and the authors said a larger patient group could help clarify this.
  • Staining intensity may depend on the molecular integrity of the tumor tissue, and its interpretation can be biased by a subjective component.
  • Only overall survival was analyzed. The data do not show when disease progression occurred, so recurrence-free survival could not be examined.
  • It remained unclear why tumors with focal expression showed worse survival than tumors with evenly distributed expression.

Topics

Medical terms in this study, explained in our Lexicon: Podoplanin (D2-40), Squamous Cell Carcinoma, Mesothelium, Mesothelioma, Prognosis, Overall Survival, Metastasis.

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