Division of Molecular Genetics and Biofunction, Institute of Regenerative Medicine and Biofunction,, Division of Pathological Biochemistry, Department of Biomedical Sciences.
Division of Molecular Genetics and Biofunction, Institute of Regenerative Medicine and Biofunction.
Eur J Dermatol. 2013 May-Jun;23(3):344-9. doi: 10.1684/ejd.2013.2021.
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.
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.
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).
Down-regulation of PITX1 expression might contribute to the progression of cutaneous malignant melanoma via promoting cell proliferative activity.
垂体同源盒 1（PITX1）蛋白是同源盒转录因子家族的一员，在人类发育过程中具有重要作用。最近，PITX1 基因被认为是多种人类癌症中的肿瘤抑制基因。
本研究探讨了 PITX1 在人类皮肤恶性黑色素瘤发生发展中的表达情况。
采用免疫组织化学和/或免疫荧光分析方法，检测 PITX1 在正常皮肤和 40 例皮肤恶性黑色素瘤（包括 10 例原位黑色素瘤）组织中的组织学表达。
正常皮肤中 PITX1 表达于黑色素细胞的细胞核内。40 例原发性皮肤恶性黑色素瘤中，PITX1 表达阳性（标记指数：≥10%）21 例（52.5%），阴性（标记指数：<10%）19 例（47.5%）。PITX1 阴性病例的平均肿瘤厚度（7.11±10.3 mm）明显高于 PITX1 阳性病例（1.90±3.19 mm）（P<0.01）。PITX1 阳性病例中发生转移的病例数为 1 例（4.76%），PITX1 阴性病例中发生转移的病例数为 7 例（36.8%）；PITX1 阴性病例的转移频率明显高于 PITX1 阳性病例（P=0.012）。此外，PITX1 表达降低与临床分期显著相关（P<0.001）。有趣的是，PITX1 表达与皮肤恶性黑色素瘤的细胞增殖呈负相关（P<0.001）。
PITX1 表达下调可能通过促进细胞增殖活性促进皮肤恶性黑色素瘤的进展。
