Increased HOX C13 expression in metastatic melanoma progression

Abstract

Background: The process of malignant transformation, progression and metastasis of melanoma is not completely understood. Recently, the microarray technology has been used to survey transcriptional differences that might provide insight into the metastatic process, but the validation of changing gene expression during metastatic transition period is poorly investigated. A large body of literature has been produced on the role of the HOX genes network in tumour evolution, suggesting the involvement of HOX genes in several types of human cancers. Deregulated paralogous group 13 HOX genes expression has been detected in melanoma, cervical cancer and odonthogenic tumors. Among these, Hox C13 is also involved in the expression control of the human keratin genes hHa5 and hHa2, and recently it was identified as a member of human DNA replication complexes.

Methods: In this study, to investigate HOX C13 expression in melanoma progression, we have compared its expression pattern between naevi, primary melanoma and metastasis. In addition HOXC13 profile pattern of expression has been evaluated in melanoma cell lines.

Results: Our results show the strong and progressive HOX C13 overexpression in metastatic melanoma tissues and cytological samples compared to nevi and primary melanoma tissues and cells.

Conclusions: The data presentated in the paper suggest a possible role of HOX C13 in metastatic melanoma switch.

Figure 1

Localization of HOX C13 protein in human hair follicles: immunopositivity (red) in cortex (co), in cuticle (cu), in hair papilla (hp), and in germinative cells (gc). Immunonegativity in medulla (me), in outer root sheath (ors), in connective sheath (cs) and inner root sheath (irs).

Figure 2

HOX C13 immunostaining in melanoma tissues. A: HOX C13 immunopositivity in hair bulb follicle as positive control (20X); B: HOX C13 immunonegativity in primary melanoma sample (40X); C: High HOX C13 immunopositivity in melanoma metastasis sample score 3+ (20X); D: High HOX C13 immunopositivity in melanoma micro-metastasis sample score 3+ (60X).

Figure 3

HOX C13 immunostaining in limphnode melanoma cytological samples. A: HOX C13 immunopositivity score 1+ (60X); B: HOX C13 immunopositivity score 2+ (60X); C: HOX C13 immunopositivity score 3+ (60X).

Figure 4

HOX C13/HMB-45 double staining IHC in primary melanoma tissues. A: HOX C13 immunonegativity in HMB-45 positive (red) primary melanoma (10X); B: details of melanoma cells in papillary dermis (20X); C: details of melanoma cells in reticular dermis (20x).

Figure 5

HOX C13/HMB-45 double staining IHC in metastatic melanoma tissues. A: Cytoplasm HMB-45 immunopositivity (red) and nuclear HOX C13 immunopositivity (brown) in nodal metastasis (20X); B: Cytoplasm HMB-45 immunopositivity (red) and nuclear HOX C13 immunopositivity (brown) in nodal subcapsular micrometastasis (40X) C: Cytoplasm HMB-45 immunopositivity (red) and nuclear HOX C13 immunopositivity (brown) in dermal metastasis (40X).

Figure 6

HOX C13 Real Time expression in primary and metastatic melanoma tissues. All reactions were performed in triplicate and data are expressed as mean of relative amount of mRNAs levels.

Figure 7

HOX C13Real Time expression in cytological melanoma samples. All reactions were performed in triplicate and data are expressed as mean of relative amount of mRNAs levels.

Figure 8

HOX C13Real Time expression in primary and metastatic cell lines. All reactions were performed in triplicate and data are expressed as mean of relative amount of mRNAs levels.