Clinicopathological features and pituitary homeobox 1 gene expression in the progression and prognosis of cutaneous malignant melanoma

Abstract

The evidence that PITX1 (pituitary homeobox 1) is a significant tumor suppressor in human cancer remains largely circumstantial, but it clearly warrants further study as little is known about the tumor-inhibitory roles of PITX1 in cutaneous malignant melanoma. The aims of this study were to investigate PITX1 gene expression in patients with cutaneous malignant melanoma and to evaluate its potential relevance to clinicopathological characteristics and tumor cell proliferation. Clinicopathological findings of patients with cutaneous malignant melanoma were analyzed retrospectively. PITX1 and Ki-67 expression were detected by immunohistochemistry in malignant melanoma and healthy tissue samples from each patient. Labeling indices were calculated based on PITX1 gene and Ki-67 expression. The correlation between PITX1and Ki-67 expressions was analyzed in cutaneous malignant melanoma cases. The relationship between PITX1 expression intensity and clinicopathological characteristics was also analyzed. PITX1 expression was observed in all (100%) normal healthy skin tissue samples. In addition, PITX1 expression was found in 56 (80%) and was absent in 14 (20%) of the 70 cutaneous malignant melanoma cases. Ki-67 positive expression was only detected in the 14 (20%) PITX1-negative cases. PITX1-positive tumor cells were observed on the surface, but Ki-67 positive tumor cells were observed in deeper zones of the tumor nests. PITX1 expression was downregulated in human cutaneous malignant melanoma lesions compared with healthy skin tissue, but Ki-67 expression was upregulated in concordance with the progression of cutaneous malignant melanoma. PITX1 expression may be involved in tumor progression and is a potential tumor suppressor gene and prognostic marker for cutaneous malignant melanoma.

Keywords: Cutaneous malignant melanoma; Ki-67; Pituitary homeobox 1; Prognosis; Proliferation.

Figure 1

Histopathological appearance of cutaneous malignant melanoma in (A) hematoxylin and eosin (H&E, ×200) and (B) immunohistochemical HMB45 positivity. B‐SA  =  3,3′‐diaminobenzidine tetrahydrochloride (×100).

Figure 2

PITX1 and Ki‐67 expression in healthy skin and cutaneous malignant melanoma samples. (A) PITX1 expression in all layers of the epidermis and skin appendages of healthy skin. (B) Ki‐67 expression in the basal layer of healthy skin epidermis. (C) PITX1 positivity in cutaneous malignant melanoma (at least 10% of tumor cells showing positive staining in the nuclei). (D) Ki‐67 negativity in cutaneous malignant melanoma (< 10% of the labeling index). (E) PITX1 negativity in cutaneous malignant melanoma (< 10% of tumor cells showing positive signals). (F) Ki‐67 positivity in cutaneous malignant melanoma (> 10% of the labeling index). B‐SA  =  3,3′‐diaminobenzidine tetrahydrochloride (A, B, ×200; C–F ×100); PITX1  =  pituitary homeobox 1.

Figure 3

(A) PITX1‐positive tumor cells on the surface of the tumor nests and (B) Ki‐67‐positive tumor cells in the deeper zone of the tumor nests in cutaneous malignant melanoma. B‐SA  =  3,3′‐diaminobenzidine tetrahydrochloride (×100); PITX1  =  pituitary homeobox 1.