Immunohistochemical and Molecular Features of Melanomas Exhibiting Intratumor and Intertumor Histomorphologic Heterogeneity

Creator(s)

Haider A. Mejbel, University of Texas MD Anderson Cancer Center
Sri Krishna C. Arudra, University of Texas MD Anderson Cancer Center
Dinesh Pradhan, University of Texas MD Anderson Cancer Center
Carlos A. Torres-Cabala, University of Texas MD Anderson Cancer Center
Priyadharsini Nagarajan, University of Texas MD Anderson Cancer Center
Michael T. Tetzlaff, University of Texas MD Anderson Cancer Center
Jonathan L. Curry, University of Texas MD Anderson Cancer Center
Doina Ivan, University of Texas MD Anderson Cancer Center
Dzifa Y. Duose, University of Texas MD Anderson Cancer Center
Raja Luthra, University of Texas MD Anderson Cancer Center
Victor G. Prieto, University of Texas MD Anderson Cancer Center
Leomar Y. Ballester, University of Texas Health Science Center at Houston
Phyu P. Aung, University of Texas MD Anderson Cancer Center

Document Type

Article

Publication Date

11-1-2019

Description

Melanoma is a heterogeneous neoplasm at the histomorphologic, immunophenotypic, and molecular levels. Melanoma with extreme histomorphologic heterogeneity can pose a diagnostic challenge in which the diagnosis may predominantly rely on its immunophenotypic profile. However, tumor survival and response to therapy are linked to tumor genetic heterogeneity rather than tumor morphology. Therefore, understating the molecular characteristics of such melanomas become indispensable. In this study, DNA was extracted from 11 morphologically distinct regions in eight formalin-fixed, paraffin-embedded melanomas. In each region, mutations in 50 cancer-related genes were tested using next-generation sequencing (NGS). A tumor was considered genetically heterogeneous if at least one non-overlapping mutation was identified either between the histologically distinct regions of the same tumor (intratumor heterogeneity) or among the histologically distinct regions of the paired primary and metastatic tumors within the same patient (intertumor heterogeneity). Our results revealed that genetic heterogeneity existed in all tumors as non-overlapping mutations were detected in every tested tumor (n = 5, 100%; intratumor: n = 2, 40%; intertumor: n = 3, 60%). Conversely, overlapping mutations were also detected in all the tested regions (n = 11, 100%). Melanomas exhibiting histomorphologic heterogeneity are often associated with genetic heterogeneity, which might contribute to tumor survival and poor response to therapy.

Copyright Statement

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Citation Information

Mejbel, Haider A.; Arudra, Sri Krishna C.; Pradhan, Dinesh; Torres-Cabala, Carlos A.; Nagarajan, Priyadharsini; Tetzlaff, Michael T.; Curry, Jonathan L.; Ivan, Doina; Duose, Dzifa Y.; Luthra, Raja; Prieto, Victor G.; Ballester, Leomar Y.; and Aung, Phyu P.. 2019. Immunohistochemical and Molecular Features of Melanomas Exhibiting Intratumor and Intertumor Histomorphologic Heterogeneity. Cancers. Vol.11(11). https://doi.org/10.3390/cancers11111714