Significance of leptin receptor expression in cell proliferation, neoangiogenesis and organization of elastic fibers in squamocellular carcinoma of the skin

[M. S. Vuletić]

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Adipokin leptin ostvaruje funkcije preko svojih transmembranskih receptora (LEPR). U brojnim malignim tumorima stimuliše rast, migraciju i invazivnost malignih ćelija. Cilj našeg rada je utvrditi značaj ekspresije receptora za leptin u ćelijskoj proliferaciji, neoangiogenezi i organizaciji elastičnih vlakana u skvamocelularnom karcinomu kože (cSCC). Korišćen je biopsijski materijal dobijen ekscizijom skvamocelularnog karcinoma kože. Ispitivanu grupu su činile ekscizione biopsije skvamocelularnog karcinoma kože (n=62), a kontrolnu grupu (n=62) su činile ekscizione biopsije netumorskog tkiva kože (iz okoline tumora). Nakon rutinske obrade i kalupljenja u parafin, na presecima debljine 4 µm su primenjene histohemijske Hematoxylin-Eosin, Verhoeff – Van Gieson i imunohistohemijska ABC metoda sa anti LEPR, Ki67, p53, CD34 i Cytokeratin AE1/AE3 antitelima. Za analizu dobijenih rezultata korišćen je statistički programski paket SPSS za Windows (26.0). LEPR ekspresija je značajno povezana sa indeksom proliferacije i mikrovaskularne gustine, histološkim gradusom tumora i količinom i karakteristikama elastičnih vlakana u peritumorskom tkivu. Izražena LEPR ekspresija je u 50% tumora udružena sa većom količinom isprekidanih i zadebljalih elastičnih vlakana, u 66,7% sa visokim indeksom proliferacije, 70% sa visokim indeksom mikrovaskularne gustine, i u 94,4% slučajeva sa loše diferentovanim cSCC. Multivarijantna regresiona analiza je pokazala da su cSCC sa izraženom LEPR ekspresijom sedam puta češće loše diferentovani od tumora sa umerenom ili LEPR ekspresijom u tragu. Naši rezultati ukazuju da je LEPR ekspresija prediktor malignog potencijala cSCC, pa je na osnovu LEPR ekspresije moguće identifikovati agresivan fenotip ovih tumora, što pruža mogućnost individualizacije antitumorskog tretmana primenom antagonista LEPR.

Adipokin leptin performs functions through its transmembrane receptors (LEPR). In numerous malignant tumors, it stimulates the growth, migration and invasiveness of malignant cells. The aim of our study was to determine the significance of leptin receptor expression in cellular proliferation, neoangiogenesis, and elastic fiber organization in squamous cell carcinoma of the skin (cSCC). Biopsy material obtained by excision of squamous cell carcinoma of the skin was used. The study group consisted of excisional biopsies of squamous cell skin cancer (n = 62), and the control group (n = 62) consisted of excisional biopsies of non-tumor skin tissue (from the tumor environment). After routine processing and molding into paraffin, histochemical HematoxylinEosin, Verhoeff - Van Gieson and immunohistochemical ABC methods with anti-LEPR, Ki67, p53, CD34 and Cytokeratin AE1 / AE3 antibodies were applied on 4 µm thick sections. The statistical software package SPSS for Windows (26.0) was used to analyze the obtained results LEPR expression is significantly associated with proliferation index and microvascular density, tumor histological grade, and the amount and characteristics of elastic fibers in peritumoral tissue. Significant LEPR expression is associated in 50% of tumors with higher amounts of ruptured and thickened elastic fibers, in 66.7% with high proliferation index, 70% with high microvascular density index, and in 94.4% of cases with poorly differentiated cSCC. Multivariate regression analysis showed that cSCCs with pronounced LEPR expression were seven times more often poorly differentiated than tumors with moderate or trace LEPR expression. Our results indicate that LEPR expression is a predictor of malignant cSCC potential, so based on LEPR expression it is possible to identify the aggressive phenotype of these tumors, which provides the possibility of individualization of antitumor treatment using LEPR antagonists.

skvamocelularni karcinom kože, LEPR ekspresija, indeks proliferacije, indeks mikrovaskularne gustine, elastična vlakna, histološki gradus, imunihistohemija

squamous cell carcinoma of the skin, LEPR expression, proliferation index, microvascular density index, elastic fibers, histological grade, immunohistochemistry

616.5-006.6(043.3)

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