Dataset Information

Expression of OPN3 in acral lentiginous melanoma and its associated with clinicohistopathologic features and prognosis.

ABSTRACT:

Background

OPN3 upregulation associated with metastasis was recently described in two subtypes of lung cancers. And OPN3 identified in light-independent functions in epidermal melanocytes has already shown promise. However, in malignant melanocytic tissues, the expression and characterization of OPN3 remain uncharacterized.

Objectives

We investigated the clinico-histopathologic features in relation to OPN3 expression of acral lentiginous melanoma (ALM), which is a rare cutaneous melanoma subtype and not associated with prior sunlight exposure.

Methods

In all, 84 samples of junctional melanocytic nevi (JMN, n = 12), primary ALMs (n = 39) and inguinal lymph node metastasis (ILNM, n = 23) from ALMs were evaluated for the immunohistochemical expression of OPN3. OPN3 messenger RNA and protein level were further determined in melanocytic tumors using quantitative real-time PCR, multiimmunofluorescence and Western blot assays. We also estimated the associations OPN3 expression between clinicopathological features and prognosis.

Results

ILNMs, in contrast to JMN and ALMs, had higher OPN3 expression scores (p < .001) by immunohistochemistry analysis. High OPN3 score was associated with presence of ulceration, increased Breslow depth and Clark level (p = .025, p = .042, and p = .012, respectively). Furthermore, a remarkable difference (p = .037) of patient overall survival was found when comparing the OPN3 expression of immunohistochemical score between equal to or larger than 100 and below 100 groups. Also, Cox regression models showed that high OPN3 scores were associated with worse melanoma survival.

Conclusion

High OPN3 expression is significantly associated with ALMs and metastatic phenotype as well as a poor prognosis.

SUBMITTER: Zeng W

PROVIDER: S-EPMC8342238 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceAcral lentiginous melanoma (ALM) is a rare subtype of malignant melanoma typically occurring on the palmar and plantar surfaces. Although it has distinctive genetic, prognostic, and behavioral characteristics relative to cutaneous melanomas overall, owing to its rarity, treatment is largely guided by data extrapolated from more common subtypes. Although sentinel lymph node (SLN) status has been shown to be a significant prognostic factor for ALM, the independent effect of ALM-subtype disease on the likelihood of SLN positivity and the stage-specific positivity rates for ALM are not well characterized.ObjectiveTo evaluate the association of ALM with SLN status as well as to characterize the clinical stage-specific rates of SLN positivity for ALM based on the AJCC Cancer Staging Manual, 8th edition (AJCC-8).Design, setting, and participantsThe National Cancer Database (NCDB) includes all reportable cases from Commission on Cancer accredited facilities and represents approximately 50% of all newly diagnosed melanoma cases in the US. This retrospective cohort study included cases of AJCC-8 clinical stage I to II melanomas from the NCDB diagnosed from 2012 to 2015. The analysis took place between April 2021 and September 2021.ExposuresMelanoma histopathologic subtype.Main outcomes and measuresSentinel lymph node status.ResultsWe identified 60 148 patients with malignant melanomas, 959 of whom had ALM-subtype disease. Among patients in the cohort, 25 550 (42.5%) were women and the mean (SD) age was 64 (16) years. Multivariable logistic regression controlling for demographic and histopathologic characteristics revealed that ALM was independently associated with the highest risk for SLN positivity among included subtypes (vs superficial spreading melanoma: odds ratio, 1.91; 95% CI, 1.59-2.28). Subgroup analysis by AJCC clinical stage demonstrated that ALM was independently associated with the highest risk for SLN positivity for both stage IB and II disease. The rate of SLN positivity for patients with stage IB and II ALM was 18.39% (95% CI, 13.82%-24.03%) and 39.53% (34.98%-44.26%), respectively.Conclusions and relevanceIn this cohort study ALM was independently associated with SLN positivity and had relatively high positivity rates at clinical stage IB and II. This suggests that SLNB should be encouraged for all patients with clinical stage IB and II ALM, and such patients should receive appropriate counseling about the higher regional metastatic risk of their cancers. Future work with a larger cohort is required to elucidate the risk of SLN positivity for stage IA ALM.