title: Mitotic rate is a more reliable unfavorable prognosticator than ulceration for early cutaneous melanoma: a 5-year survival analysis.
abstract: The presence of ulceration has been considered as one of the most important primary tumor characteristics of cutaneous malignant melanoma (CMM) for predicting patient outcome. Yet recently, scientific attention has been drawn towards another microscopic feature of primary tumors, the mitotic rate (MR). The present study aimed to examine the relationship between the presence of ulceration and the mitotic rate and clinicopathological characteristics and melanoma patient survival, and to discuss the results in the context of AJCC melanoma staging recommendations. Tissue samples were obtained from 104 patients treated for CMM. In classical H&E staining, the mitotic rate and the presence of ulceration were evaluated. Non-mitogenic tumors were defined as having 0 mitoses/mm2, low mitogenic potential, 1-2 mitoses/mm2 and highly mitogenic tumors, ≥3 mitoses/mm2. In the entire group of 104 patients, a high mitotic rate (hMR) and ulceration were highly negative prognostic factors, and indicated considerably shorter overall survival, cancer-specific overall survival and disease-free survival. Notably, hMR appeared to have a statistically significant negative impact on survival in early melanomas in both the pT1 (P=0.001) and pT2 subgroups (P=0.006). Kaplan‑Meier analysis of the remaining subsets (pT3 and pT4) did not reveal any important differences in the 5-year survival with regard to MR values. The presence of ulceration also had a prognostic significance for early melanomas, but only for pT1 tumors (P=0.05). Multivariate analysis confirmed that hMR was strongly associated with an unfavorable prognosis. Ulceration had no prognostic significance in the Cox proportional hazards model. Considering the biology of melanoma, hMR seems to be a more reliable parameter than the presence of ulceration. The value of MR categorizes melanomas into tumors with low or high proliferative potential, thus giving direct information concerning their capacity to infiltrate deeper layers of the dermis and, potentially, to generate regional lymph node and distant metastases.
authors.affiliation: Department of Pathomorphology and Oncological Cytology, Wrocław Medical University, 50‑556 Wrocław, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Donizy
authors.affiliation: Department of Pathomorphology and Oncological Cytology, Wrocław Medical University, 50‑556 Wrocław, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Kaczorowski
authors.affiliation: Department of Statistics, Wrocław University of Economics, 53-345 Wrocław, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Leskiewicz
authors.affiliation: Lower Silesian Oncology Centre, 53-413 Wrocław, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Zietek
authors.affiliation: Department of Oncology and Division of Surgical Oncology, Wrocław Medical University, 53-413 Wrocław, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Pieniazek
authors.affiliation: Department of Statistics, Wrocław University of Economics, 53-345 Wrocław, Poland.
authors.forename: Cyprian
authors.initials: C
authors.lastname: Kozyra
authors.affiliation: Department of Pathomorphology and Oncological Cytology, Wrocław Medical University, 50‑556 Wrocław, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Halon
authors.affiliation: Lower Silesian Oncology Centre, 53-413 Wrocław, Poland.
authors.forename: Rafal
authors.initials: R
authors.lastname: Matkowski
mesh_terms: D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D008938:Mitosis; D008940:Mitotic Index; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D012878:Skin Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D000096142:Cutaneous Malignant Melanoma