title: Golgi-Related Proteins GOLPH2 (GP73/GOLM1) and GOLPH3 (GOPP1/MIDAS) in Cutaneous Melanoma: Patterns of Expression and Prognostic Significance.
abstract: GOLPH2 and GOLPH3 are Golgi-related proteins associated with aggressiveness and progression of a number of cancers. Their prognostic significance in melanoma has not yet been analyzed. We performed immunohistochemical analysis for GOLPH2 and GOLPH3 in 20 normal skin, 30 benign nevi and 100 primary melanoma tissue samples and evaluated their expression in three compartments: cancer cells, tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs). High levels of both proteins in melanoma cells were associated with characteristics of aggressive disease, and shorter disease-free survival (DFS) and cancer-specific overall survival (CSOS). On the contrary, increased numbers of GOLPH2-positive and GOLPH3-positive TAMs were observed in thinner, non-ulcerated tumors, with brisk lymphocytic reaction and absent lymphangioinvasion. Distant metastases were not observed among patients with high numbers of GOLPH2-positive TAMs. Increased expression of either protein in TAMs was related to prolonged CSOS and DFS. Similarly, GOLPH3-expressing CAFs were more frequent in thin melanomas with low mitotic rate, without ulceration and lymphangioinvasion. Moreover, increased GOLPH3-positive CAFs correlated with the absence of regional or distant metastases, and with longer CSOS and DFS. GOLPH2 expression was not observed in CAFs. Our results suggest that GOLPH2 and GOLPH3 play a role in melanoma progression and are potential targets for molecular-based therapies.
authors.affiliation: Department of Pathomorphology and Oncological Cytology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland. piotrdonizy@wp.pl.
authors.forename: Piotr
authors.initials: P
authors.lastname: Donizy
authors.affiliation: Department of Pathomorphology and Oncological Cytology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland. octopuso@wp.pl.
authors.forename: Maciej
authors.initials: M
authors.lastname: Kaczorowski
authors.affiliation: Faculty of Mathematics and Information Science, Warsaw University of Technology, Koszykowa 75, 00-662 Warsaw, Poland. przemyslaw.biecek@gmail.com.
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Biecek
authors.affiliation: Department of Pathomorphology and Oncological Cytology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland. ahalon2@gmail.com.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Halon
authors.affiliation: Department of Pathomorphology and Oncological Cytology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland. tszkudlarek@poczta.fm.
authors.forename: Teresa
authors.initials: T
authors.lastname: Szkudlarek
authors.affiliation: Department of Oncology, Wroclaw Medical University; pl. Hirszfelda 12, 53-413 Wroclaw, Poland. rem@onet.pl.|Lower Silesian Cancer Center, Hirszfelda 12, 53-413 Wroclaw, Poland. rem@onet.pl.
authors.forename: Rafal
authors.initials: R
authors.lastname: Matkowski
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D011379:Prognosis; D012867:Skin / Q000378:metabolism; D012878:Skin Neoplasms; D000096142:Cutaneous Malignant Melanoma
chemical_list: D014408:Biomarkers, Tumor; C410824:GOLM1 protein, human; C429024:GOLPH3 protein, human; D008565:Membrane Proteins
keywords: GOLPH2; GOLPH3; cancer-associated fibroblasts; melanoma; tumor-associated macrophages