Different Serotonergic Expression in Nevomelanocytic Tumors

Clara Naimi-Akbar,Markus Ritter,Sasika Demel,Husameldin El-Nour,Efrain C Azmitia,Klas Nordlind,Mari-Anne Hedblad

doi:10.3390/cancers2021166

Clara Naimi-Akbar, Markus Ritter + Show 5 more

Open Access

https://doi.org/10.3390/cancers2021166

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Abstract

The neuromediator serotonin (5-hydroxytryptamine; 5-HT) has been proposed to play a role in tumor progression. Thus, the aim of the present investigation was to determine whether alterations in the serotonergic system occur in nevomelanocytic tumors. For this purpose, paraffin-embedded biopsies of superficial spreading malignant melanoma (SSM), dysplastic compound nevi (DN) and benign compound nevi (BCN) were characterized with regard to their expression of 5-HT, the 5-HT1A and 5-HT2A receptors, and the serotonin transporter protein (SERT), by immunohistochemical analysis. Melanocytes in the region surrounding the tumor were found to express both the 5-HT1A and 5-HT2A receptors. Tumor cells that immunostained positively for the different serotonergic markers were observed in the suprabasal epidermis of DN tissue and, to an even greater extent, in the case of SSM. Furthermore, some of these latter cells expressed both 5-HT1AR and 5-HT2AR. The level of expression of 5-HT1AR at the junctional area was lower for SSM than for DN or BCN. As the degree of atypia increased, the intensity of tumor cell staining in the dermis for 5-HT1AR and SERT declined. Vessel immunoreactivity for 5-HT2A was more intense in SSM than in BCN tissue. Round-to-dendritic cells that expressed both SERT and 5-HT1AR were seen to infiltrate into the dermal region of the tumor, this infiltration being more evident in the case of DN and SSM. These latter cells were also tryptase-positive, indicating that they are mast cells. Thus, alterations in serotonergic system may be involved in nevomelanocytic tumors and mast cells may play an important role in this connection.

Highlights

Progression of a tumor to cutaneous malignant melanoma begins with the loss of cell cycle control and dysregulated proliferation of intraepidermal melanocytes
The frequency of 5-HT positive cells in the suprabasal epidermis increased in the order benign compound nevi (BCN) < dysplastic compound nevi (DN) < superficial spreading malignant melanoma (SSM) (P < 0.05)
The expression of the 5-HT1A and 2A receptors in this region was lower in BCN than in SSM, and DN, tissue (P < 0.05 in each case)

Summary

Introduction

Progression of a tumor to cutaneous malignant melanoma begins with the loss of cell cycle control and dysregulated proliferation of intraepidermal melanocytes. Serotonin (5-hydroxytryptamine; 5-HT) participates in the regulation of a wide variety of physiological processes [1], including basic cell functions such as proliferation, differentiation/maturation, migration and maintenance of vessel tonus [2]. Of the 21 different receptor (R) subtypes to 5-HT that have been cloned in mammals to date [1,3], the 5-HT1AR is one of the most extensively characterized. This receptor is present both presynaptically, as an autoreceptor on raphe cells, located on the midline of the brainstem, and postsynaptically on target neurons located in the hippocampus. The 5-HT1AR has been proposed to promote cell differentiation, while the opposite effect has been reported for the 5-HT2 receptor family [2]

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