Background: The pituitary homeobox 1 (PITX1) protein is a member of the bicoid-related homeobox transcription factors and has essential roles in human development. Recently, the PITX1 gene has been considered as a tumor suppressor gene in various human cancers.
Objective: This study examined the expression of PITX1 in the development and progression of human cutaneous malignant melanoma.
Materials & methods: Immunohistochemical and/or immunofluorescence analyses were performed to examine the histological expression of PITX1 in healthy skin and 40 cutaneous malignant melanoma cases, including 10 melanoma in situ cases.
Results: Expression of PITX1 was shown in nuclei of melanocytes in normal skin. PITX1 expression was positive (labeling index: ≥10%) in 21 (52.5%) cases and negative (labeling index: <10%) in 19 (47.5%) of 40 cases of primary cutaneous malignant melanoma. The mean tumor thickness in PITX1-negative cases (7.11 ± 10.3 mm) was significantly higher than that in the positive cases (1.90 ± 3.19 mm) (P<0.01). The numbers of cases showing metastasis were 1 (4.76%) of 21 cases in PITX1-positive cases and 7 (36.8%) of 19 cases in PITX1-negative cases; the frequency was significantly higher in PITX1-negative cases than the positive cases (P = 0.012). Moreover, the reduction in PITX1 expression correlated significantly with clinical stage (P<0.001). Interestingly, PITX1 expression was inversely correlated with cell proliferation of cutaneous malignant melanoma (P<0.001).
Conclusions: Down-regulation of PITX1 expression might contribute to the progression of cutaneous malignant melanoma via promoting cell proliferative activity.
Keywords: Ki-67; PITX1; malignant melanoma; tumor progression.