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The Ras Gene02:38

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The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
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Prognostic Significance of RAS Mutations and P53 Expression in Cutaneous Squamous Cell Carcinomas.

Manuel António Campos1,2,3,4, Sofia Macedo1,2, Margarida Sá Fernandes5

  • 1Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal.

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Summary

RAS mutations are linked to aggressive features in cutaneous squamous cell carcinoma (cSCC). While p53 overexpression predicts recurrence, further studies are needed to confirm prognostic significance in high-risk patients.

Keywords:
RASbiomarkercutaneous squamous cell carcinomaexpressionmetastasesmutationoutcomep53prognosisprognostic biomarkerrecurrence

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Area of Science:

  • Oncology
  • Dermatology
  • Molecular Biology

Background:

  • TP53 gene alterations are frequent in cutaneous squamous cell carcinoma (cSCC).
  • RAS mutations are infrequently reported in cSCC, with limited understanding of their role.

Purpose of the Study:

  • To determine the frequency of p53 expression and RAS mutations in cSCC.
  • To correlate these molecular findings with clinicopathological features and patient outcomes.
  • To assess the predictive value of p53 expression and RAS mutations for cSCC progression.

Main Methods:

  • Retrospective analysis of cSCC cases.
  • Immunohistochemistry was used to evaluate p53 expression.
  • Genetic profiling was performed to identify RAS mutations.
  • Logistic regression models were employed to assess predictive values.

Main Results:

  • RAS mutations were found in 9.3% of cSCC cases.
  • p53 overexpression was observed in 82.1% of cases.
  • RAS mutations were more common in invasive cSCC (10.7%) than in situ cSCC (3.2%).
  • RAS mutations correlated with an infiltrative pattern of invasion (p=0.046).
  • p53 overexpression was a univariate predictor of recurrence.

Conclusions:

  • RAS mutations are associated with local aggressiveness in cSCC.
  • p53 overexpression may serve as a prognostic marker for recurrence.
  • Larger studies are required to establish the prognostic significance of p53 in risk stratification for recurrent and metastatic cSCC.