SF3B1, NRAS, KIT, and BRAF Mutation; CD117 and cMYC Expression; And tumoral pigmentation in sinonasal melanomas

An analysis with newly found molecular alterations and some population-based molecular differences

Joanna P. Wroblewska, Jason Mull, Cheng-Lin Wu, Masakazu Fujimoto, Toru Ogawa, Andrzej Marszalek, Mai P. Hoang

Research output: Contribution to journalArticle

Abstract

Sinonasal melanomas encompass melanoma arising in the nasal cavity and paranasal sinuses. Despite recent advances in tumor genomics, correlation between mutational status and protein expression with prognosis and tumor pigmentation has not been carried out in sinonasal melanomas. Ninety-five sinonasal melanomas from 95 patients were included. As per univariate analyses, age was the only variable that significantly correlated with progression-free survival. SF3B1, NRAS, KIT, and BRAF mutations were documented in 7% (5/72), 22% (16/72), 22% (16/72), and 8% (6/72) of cases, respectively. Comutation was detected in 6 cases: NRAS and KIT in 2 cases; NRAS and BRAF in 2 cases; SF3B1, KIT, and BRAF in one case; and SF3B1, NRAS, and KIT in one case. Correlations approaching statistical significance were observed between BRAF mutation status and poorer overall survival and progression-free survival (log-rank P-values=0.054 and 0.061). Increased CD117 expression (33%, 29/88) and decreased nuclear cMYC expression (40%, 39/84) significantly correlated with cytoplasmic pigmentation. Several SF3B1, NRAS, and KIT mutations not previously documented in sinonasal melanomas were detected in our series, suggesting a potential role for targeted therapies. A similar frequency of SF3B1, NRAS, and KIT mutations was noted in Asian cases, whereas NRAS, KIT, and BRAF mutations were predominant in the United States and European cases; however, the number of included cases was small. The significant association between CD117 and cMYC expression with increased cytoplasmic pigmentation in our series suggests that the pigmented morphologic appearance of sinonasal melanomas could be attributed to the underlying oncogenic mutations and metabolic interaction.

Original languageEnglish
Pages (from-to)168-177
Number of pages10
JournalAmerican Journal of Surgical Pathology
Volume43
Issue number2
DOIs
Publication statusPublished - 2019 Feb 1

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Pigmentation
Melanoma
Mutation
Population
Paranasal Sinuses
Disease-Free Survival
Nasal Cavity
Genomics
Neoplasms
Survival
Proteins

All Science Journal Classification (ASJC) codes

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine

Cite this

@article{534684fe5f284817843f78db5fead116,
title = "SF3B1, NRAS, KIT, and BRAF Mutation; CD117 and cMYC Expression; And tumoral pigmentation in sinonasal melanomas: An analysis with newly found molecular alterations and some population-based molecular differences",
abstract = "Sinonasal melanomas encompass melanoma arising in the nasal cavity and paranasal sinuses. Despite recent advances in tumor genomics, correlation between mutational status and protein expression with prognosis and tumor pigmentation has not been carried out in sinonasal melanomas. Ninety-five sinonasal melanomas from 95 patients were included. As per univariate analyses, age was the only variable that significantly correlated with progression-free survival. SF3B1, NRAS, KIT, and BRAF mutations were documented in 7{\%} (5/72), 22{\%} (16/72), 22{\%} (16/72), and 8{\%} (6/72) of cases, respectively. Comutation was detected in 6 cases: NRAS and KIT in 2 cases; NRAS and BRAF in 2 cases; SF3B1, KIT, and BRAF in one case; and SF3B1, NRAS, and KIT in one case. Correlations approaching statistical significance were observed between BRAF mutation status and poorer overall survival and progression-free survival (log-rank P-values=0.054 and 0.061). Increased CD117 expression (33{\%}, 29/88) and decreased nuclear cMYC expression (40{\%}, 39/84) significantly correlated with cytoplasmic pigmentation. Several SF3B1, NRAS, and KIT mutations not previously documented in sinonasal melanomas were detected in our series, suggesting a potential role for targeted therapies. A similar frequency of SF3B1, NRAS, and KIT mutations was noted in Asian cases, whereas NRAS, KIT, and BRAF mutations were predominant in the United States and European cases; however, the number of included cases was small. The significant association between CD117 and cMYC expression with increased cytoplasmic pigmentation in our series suggests that the pigmented morphologic appearance of sinonasal melanomas could be attributed to the underlying oncogenic mutations and metabolic interaction.",
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SF3B1, NRAS, KIT, and BRAF Mutation; CD117 and cMYC Expression; And tumoral pigmentation in sinonasal melanomas : An analysis with newly found molecular alterations and some population-based molecular differences. / Wroblewska, Joanna P.; Mull, Jason; Wu, Cheng-Lin; Fujimoto, Masakazu; Ogawa, Toru; Marszalek, Andrzej; Hoang, Mai P.

In: American Journal of Surgical Pathology, Vol. 43, No. 2, 01.02.2019, p. 168-177.

Research output: Contribution to journalArticle

TY - JOUR

T1 - SF3B1, NRAS, KIT, and BRAF Mutation; CD117 and cMYC Expression; And tumoral pigmentation in sinonasal melanomas

T2 - An analysis with newly found molecular alterations and some population-based molecular differences

AU - Wroblewska, Joanna P.

AU - Mull, Jason

AU - Wu, Cheng-Lin

AU - Fujimoto, Masakazu

AU - Ogawa, Toru

AU - Marszalek, Andrzej

AU - Hoang, Mai P.

PY - 2019/2/1

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N2 - Sinonasal melanomas encompass melanoma arising in the nasal cavity and paranasal sinuses. Despite recent advances in tumor genomics, correlation between mutational status and protein expression with prognosis and tumor pigmentation has not been carried out in sinonasal melanomas. Ninety-five sinonasal melanomas from 95 patients were included. As per univariate analyses, age was the only variable that significantly correlated with progression-free survival. SF3B1, NRAS, KIT, and BRAF mutations were documented in 7% (5/72), 22% (16/72), 22% (16/72), and 8% (6/72) of cases, respectively. Comutation was detected in 6 cases: NRAS and KIT in 2 cases; NRAS and BRAF in 2 cases; SF3B1, KIT, and BRAF in one case; and SF3B1, NRAS, and KIT in one case. Correlations approaching statistical significance were observed between BRAF mutation status and poorer overall survival and progression-free survival (log-rank P-values=0.054 and 0.061). Increased CD117 expression (33%, 29/88) and decreased nuclear cMYC expression (40%, 39/84) significantly correlated with cytoplasmic pigmentation. Several SF3B1, NRAS, and KIT mutations not previously documented in sinonasal melanomas were detected in our series, suggesting a potential role for targeted therapies. A similar frequency of SF3B1, NRAS, and KIT mutations was noted in Asian cases, whereas NRAS, KIT, and BRAF mutations were predominant in the United States and European cases; however, the number of included cases was small. The significant association between CD117 and cMYC expression with increased cytoplasmic pigmentation in our series suggests that the pigmented morphologic appearance of sinonasal melanomas could be attributed to the underlying oncogenic mutations and metabolic interaction.

AB - Sinonasal melanomas encompass melanoma arising in the nasal cavity and paranasal sinuses. Despite recent advances in tumor genomics, correlation between mutational status and protein expression with prognosis and tumor pigmentation has not been carried out in sinonasal melanomas. Ninety-five sinonasal melanomas from 95 patients were included. As per univariate analyses, age was the only variable that significantly correlated with progression-free survival. SF3B1, NRAS, KIT, and BRAF mutations were documented in 7% (5/72), 22% (16/72), 22% (16/72), and 8% (6/72) of cases, respectively. Comutation was detected in 6 cases: NRAS and KIT in 2 cases; NRAS and BRAF in 2 cases; SF3B1, KIT, and BRAF in one case; and SF3B1, NRAS, and KIT in one case. Correlations approaching statistical significance were observed between BRAF mutation status and poorer overall survival and progression-free survival (log-rank P-values=0.054 and 0.061). Increased CD117 expression (33%, 29/88) and decreased nuclear cMYC expression (40%, 39/84) significantly correlated with cytoplasmic pigmentation. Several SF3B1, NRAS, and KIT mutations not previously documented in sinonasal melanomas were detected in our series, suggesting a potential role for targeted therapies. A similar frequency of SF3B1, NRAS, and KIT mutations was noted in Asian cases, whereas NRAS, KIT, and BRAF mutations were predominant in the United States and European cases; however, the number of included cases was small. The significant association between CD117 and cMYC expression with increased cytoplasmic pigmentation in our series suggests that the pigmented morphologic appearance of sinonasal melanomas could be attributed to the underlying oncogenic mutations and metabolic interaction.

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