Ekspresija HDAC2 u Spitz tumorima kože

  • Ljubica Bakić Univerzitet u Beogradu, Medicinski fakultet, Integrisane akademske studije
  • Marko Barović Univerzitet u Beogradu, Medicinski fakultet, Integrisane akademske studije
  • Filip Milisavljević Univerzitet u Beogradu, Medicinski fakultet, Integrisane akademske studije
  • Martina Bosić Institut za patologiju, Medicinski fakultet Univerziteta u Beogradu

Sažetak


UVOD. Atipični Spitz nevusi predstavljaju značajan dijagnostički problem u dermatopatologiji. Nepostojanje jasnih histoloških kriterijuma i pouzdanog imunohistohemijskog markera otežava njihovo dalje određivanje prema Spitz nevusu, benignom tumoru i spicoidnom melanomu. Značaj ekspresije histon deacetilaze 2 (HDAC2) u Spic tumorima do sada nije ispitivan.

CILJ. Utvrditi nivo ekspresije HDAC2 u Spitz tumorima i ispitati razlike u ekspresiji u odnosu na kliničke (pol i starost pacijenata, lokalizacija i veličina tumora) i histopatološke parametre (histološki tip, debljina, dubina invazije i mitotska aktivnost).

MATERIJAL I METODE. Istraživanjem je obuhvaćeno 78 slučajeva sa histopatološkim dijagnozama Spitz nevusa, atipičnog Spitz nevusa, superficijalnog atipičnog Spitz nevusa i spicoidnog melanoma. Uzorci su bojeni imunohistohemijskom metodom, uz upotrebu anti-HDAC2 antitela. Ekspresija HDAC2 je analizirana unutar tri komponente tumora (epidermalna, površna i duboka dermalna) u odnosu na kliničke i histopatološke karakteristike.

REZULTATI. U uzorcima Spitz tumora primećena je uglavnom visoka ekspresija HDAC2 (> 74%). Razlike u ekspresiji u odnosu na kliničke parametre nisu uočene. Uočena je umereno jaka pozitivna korelacija među komponentama tumora: epiderma i površnog derma (r = 0,53; p = 0,004), epiderma i dubokog derma (r = 0,60; p = 0,04), kao i površnog i dubokog derma (r = 0,68; p < 0,001). Nije uočena razlika u ekspresiji HDAC2 među histološkim tipovima Spitz tumora, niti je ekspresija bila povezana sa histološkim prognostičkim parametrima spicoidnih melanoma.

ZAKLJUČAK. Ekspresija HDAC2 u Spitz tumorima je visoka i homogena u svim delovima tumora. Ne postoji značajna razlika u ekspresiji HDAC2 među različitim histološkim tipovima Spic tumora.

KLJUČNE REČI: Spitz nevus, atipični Spitz nevus, spicoidni melanom, histon deacetilaza

Biografija autora

Martina Bosić, Institut za patologiju, Medicinski fakultet Univerziteta u Beogradu
Asistent, Specijalista patologija

Reference

Spitz S. Melanomas of childhood. Am J Pathol. 1948; 24:591–609.

Luo S, Sepehr A, Tsao H. Spitz nevi and other Spitzoid lesions: Part I. Background and Diagnoses. J Am Acad Dermatol. 2011; 65(6): 1073–1084.

Requena C, Botella R, Nagore E. Characteristics of spitzoid melanoma and clues for differential diagnosis with spitz nevus. Am J Dermatopathol. 2012; 34(5):478-86.

Kapur P, Selim MA, Roy LC, Yegappan M, Weinberg AG, Hoang MP. Spitz nevi and atypical Spitz nevi/tumors: a histologic and immunohistochemical analysis. Mod Pathol. 2005; 18:197–204.

Harvell JD, Bastian BC, LeBoit PE. Persistent (recurrent) Spitz nevi: a histopathologic, immunohistochemical, and molecular pathologic study of 22 cases. Am J Surg Pathol. 2002; 26:654–61.

Rode J, Williams RA, Jarvis LR, Dhillon AP, Jamal O. S100 protein, neurone specific enolase, and nuclear DNA content in Spitz naevus. J Pathol. 1990; 161:41–5.

Yazdan P, Cooper C, Sholl LM et al. Comparative analysis of atypical spitz tumors with heterozygous versus homozygous 9p21 deletions for clinical outcomes, histomorphology, BRAF mutation, and p16 expression. Am J Surg Pathol. 2014; 38(5):638–645.

Cress WD, Seto E. Histone deacetylases, transcriptional control, and cancer. J Cell Physiol. 2000; 184:1–16.

Mehdi O, Françoise S, Sofia CL et al. HDAC gene expression in pancreatic tumor cell lines following treatment with the HDAC inhibitors panobinostat (LBH589) and trichostatine (TSA). Pancreatology. 2012; 12:146–155.

Chang HH, Chiang CP, Hung HC, Lin CY, Deng YT, Kuo MYP. Histone deacetylase 2 expression predicts poorer prognosis in oral cancer patients. Oral Oncology. 2009; 45:610–614.

Giaginis C, Alexandrou P, Delladetsima I, Giannopoulou I, Patsouris E, Theocharis S, Clinical significance of histone deacetylase (HDAC)-1, HDAC-2, HDAC-4, and HDAC-6 expression in human malignant and benign thyroid lesions. Tumor Biol. 2014; 35:61–71.

Jung KH, Noh JH, Kim JK et al. HDAC2 overexpression confers oncogenic potential to human lung cancer cells by deregulating expression of apoptosis and cell cycle proteins. J Cell Biochem. 2012; 113:2167–2177.

Song J, Noh JH, Lee JH et al. Increased expression of histone deacetylase 2 is found in human gastric cancer. APMIS. 2005; 113(4):264–8.

Benard A, Goossens-Beumer IJ, van Hoesel AQ et al. Nuclear expression of histone deacetylases and their histone modifications predicts clinical outcome in colorectal cancer. Histopathology. 2015; 66:270–282.

Quint K, Agaimy A, Di Fazio P et al. Clinical significance of histone deacetylases 1, 2, 3, and 7: HDAC2 is an independent predictor of survival in HCC. Virchows Arch. 2011; 459:129–139.

Du X, Zhao H, Zang L et al. Overexpression of Histone Deacetylase 2 Predicts Unfavorable Prognosis in Human Gallbladder Carcinoma. Pathol. Oncol. Res. 2013; 19:397–403.

Patani N, Jiang WG, Newbold RF, Mokbel K. Histonemodifier gene expression profiles are associated with pathological and clinical outcomes in human breast cancer. Anticancer Res. 2011; 31:4115–4125.

Hrzenjak A, Moinfar F, Kremser ML et al. Valproate inhibition of histone deacetylase 2 affects differentiation and decreases proliferation of endometrial stromal sarcoma cells. Mol Cancer Therapeut. 2006; 5(9):2203–10.

Weichert W. HDAC expression and clinical prognosis in human malignancies.Cancer Lett. 2009; 280: 168–76.

Spiegel S, Milstien S, Grant S. Endogenous modulators and pharmacological inhibitors of histone deacetylases in cancer therapy. Oncogene. 2012; 31:537–551.

Lott JP, Wititsuwannakul J, Lee JJ et al. Clinical characteristics associated with Spitz nevi and Spitzoid malignant melanomas: the Yale University Spitzoid Neoplasm Repository experience, 1991 to 2008. J Am Acad Dermatol.2014; 71(6):1077-82.

Benito Campos B, Bermejo J L, Han L et al. Expression of nuclear receptor corepressors and class I histone deacetylases in astrocytic gliomas. Cancer Science 2011; 102(2): 387-392.

Ashktorab H, Belgrave K, Hosseinkhah F et al. Global Histone H4 Acetylation and HDAC2 Expression in Colon Adenoma and Carcinoma.Dig Dis Sci. 2009; 54(10):2109–2117.

Weichert W, Röske A, Gekeler V et al. Histone deacetylases 1, 2 and 3 are highly expressed in prostate cancer and HDAC2 expression is associated with shorter PSA relapse time after radical prostatectomy. Br J Cancer.2008; 98(3):604-10.

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2016/12/31
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