Kliničko-patološki čimbenici i značajke staničnog ciklusa u predviđanju ishoda melanoma kože

Nola, Ivana (2005) Kliničko-patološki čimbenici i značajke staničnog ciklusa u predviđanju ishoda melanoma kože. PhD thesis, Sveučilište u Zagrebu.

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Abstract

INTRODUCTION. Malignant melanoma of the skin arises due to neoplastic transformation of melanocytes. Its behavior is characterized not so much by the local agressiveness of the primary tumor but rather by the pronounced and often vary early tendency to produce lymphogenous and /or hematogenous metastases. Management of malignant melanoma is primarly surgical excision, and the other therapeutical possibilites include chemotherapy, radiotherapy and immunotherapy in dependance of stage of disease. The last few years there is better rate survival as the result of early diagnosis. Hovever, the recent studies have been focused od determining reliable prognostic parameters that would allow more reliable predictible course of diseases with modification of therapy. The aim of this study was to determine the most important clinical and pathohistological parameters that influence the prognosis and outcome of patients with SSM and MN stage III, IV and V according to Clark and Breslow, in order offer them the most suitable form of therapy. Moreover, it was designed to assess the clinical significance of DNA content analysis by flow cytometry. MATERIALS AND METHODS. Hundred cases of malignant melanoma, diagnosed between 1992 and 2002 were selected. In order to assess the influence of the various prognostic factors on survival, the study included clinical and pathohistological parameters as well as the results of flow cytometric DNA analysis of paraffin-embedded tumor samples from all cases. Clinicopathological parameters focused on the age and sex of patients, tumor localisation, histological level of tumor progression, tumor thickness according to Breslow and mitotic rate, while flow cytometric DNA analysis comprised DNA ploidy and proliferative activity. RESULTS. Five year survival of our selected population of patients was 72%. The results of statistical analysis confirmed that statistically significant prognostic parameters for group of SSM included tumor thickness according to Breslow (p=0,0002) and mitotic rate (p=0,049). The group of MN included sex of the patient (p=0,053), histological level of tumor invasion (p=0,041), and combined analysis of flow citometry (p=0,038). In group of all specimens statistically significant prognostic parameters were histological level of tumor progression according to Clark (p=0,040), tumor thickness according to Breslow (p=0,0004) and mitotic rate (p=0,017). CONCLUSION. Depending of histological tumor type, sex of the patient, histological level of tumor progression according to Clark, tumor thickness according to Breslow, mitotic rate and combined analysis of flow citometry are considered to be the parameters of crucial relevance for the prognosis of patients with malignant melanoma of the skin. The histological level of tumor progression according to Clark, tumor thickness according to Breslow and mitotic rate were proven to be independent statistically significant parameters relevant for the outcome of patients with this disease.

Abstract in Croatian

UVOD. Maligni melanom kože nastaje malignom transformacijom melanocita. Karakterizira ga lokalna agresivnost, i sklonost ranom limfogenom i/ili hematogenom metastaziranju. Terapija malignog melanoma provodi se prvenstveno kirurški, dok se drugi oblici terapija koji uključuju kemoterapiju, radioterapiju i imunoterapiju primijenjuju ovisno o stadiju bolesti. Iako se nekoliko posljednjih godina bilježi bolje preživljenje, što je rezultat dijagnoze u ranoj fazi bolesti, i dalje se nastoje naći prognostički pokazatelji koji bi omogućili pouzdanije predviđanje tijeka bolesti uz modifikaciju terapije. Stoga je svrha ovog rada bila utvrditi koji klinički i patohistološki parametri imaju ulogu u prognozi bolesnika s SSM i MN koji po Clarku i Breslowu spadaju u III, IV i V stupanj. Ujedno se željelo ustanoviti značenje određivanja DNA sadržaja protočnom citometrijom i da li nam i taj pokazatelj može pomoći u određivanju prognoze kod bolesnika s malignim melanomom. MATERIJALI I METODE. Studija je uključila 100 bolesnika s malignim melanomom kože u razdoblju od 1992. do 2002. godine. Interes istraživanja obuhvatio je kliničke i patohistološke pokazatelje, te analizu DNA sadržaja dobivenu protočnom citometrijom iz tumorskog tkiva uklopljenog u parafinske blokove. Ispitivanjem se željelo pokazati koji od tih pokazatelja ima najvažniju ulogu u preživljenju bolesnika. Od kliničko-patoloških pokazatelja ispitivani su dob i spol bolesnika, lokalizacija tumora, histološka razina invazije, debljina tumora i mitotski indeks. Analiza DNA sadržaja protočnom citometrijom obuhvatila je određivanje ploidnosti tumora i proliferativnu aktivnost. REZULTATI. Ukupno petogodišnje preživljenje bolesnika iznostilo je 72%. Statistički značajnim pokazateljima utvrđeni su spol bolesnika za MN (p=0,053), histološka razina invazije po Clarku za MN (p=0,041) i ukupan uzorak (0,040), debljina tumora kod SSM (p=0,0002) i ukupnog uzorka (p=0,0004), mitotski indeks kod SSM (p=0,049) i ukupnog uzorka (p=0,017), te kombinirani nalaz protočne citometrije kod MN (p=0,038). ZAKLJUČAK. Ovisno o histološkom tipu tumora spol, histološka razina invazije, debljina tumora i mitotski indeks važni su za prognozu bolesnika s malignim melanomom kože, dok neovisno o histološkom tipu tumora u prognozi bolesnika ulogu ima histološka razina invazije kože, debljina tumora i mitotski indeks.

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