Decreased expression of TFPI-2 correlated with increased expression of CD133 in cholangiocarcinoma

Abstract

Background: Recent findings suggest decreasing TFPI-2 expression plays a significant role in inhibiting cell migration and tumor invasion. The clinicopathological significance of the expression of TFPI-2 and its possible correlation with the expression of CD133 in cholangiocarcinoma remains to be solved.

Methods: We investigated if TFPI-2 was involved in the clinicopathological significance of cholangiocarcinoma. An immunohistochemical method was used to detect 218 cases of cholangiocarcinoma, 30 para-neoplastic and 20 normal bile ducts for their expression status of TFPI-2 and CD133, and then the results were analyzed with the patient's age, sex, tumor site and the histological grade, clinical stage as well as overall mean survival time.

Results: Compared with the para-neoplastic and normal cholangiocytes, the expression of TFPI-2 was obviously decreased while the expression of CD133 in carcinoma cells was increased. Carcinomas with low expression of TFPI-2 were significantly corresponding to the tumor site (P = 0.006), size (P = 0.005), histological grade (P = 0.0001) and clinical stage (P = 0.0001), but not to the age (P = 0.066) and sex (P = 0.411), respectively. By Kaplan-Meier survival analysis, the low expression of TFPI-2 was significantly correlative with the overall survival time (P = 0.0001). Further, the expression of TFPI-2 was found inversely correlative with the expression of CD133 (g = -0.3876, P < 0.0001).

Conclusions: Our finding suggests that the decreased expression of TFPI-2 may play an important role in the carcinogenesis and progression, and may become a new adjunct marker in the diagnosis and prognosis in cholangiocarcinoma. The expression of TFPI-2 may be inversely correlative with the expression of CD133.

Keywords: CD133; Cholangiocarcinoma; TFPI-2; immunohistochemistry; prognosis.

Figure 1

Expression of TFPI-2 in cholangiocarcinoma. TFPI-2 was lowly expressed positive in the membrane and cytoplasm of cancer cells in cholangiocarcinoma. (TFPI-2 ×400).

Figure 2

Kaplan-Meier survival analysis by TFPI-2 status (n = 218). The y-axis represents the percentage of patients; the x-axis, their survival in months. The green line represents TFPI-2- high expressive patients with a trend of better survival than the blue line representing TFPI-2- low expressive patients (Log rank = 45.149; P = 0.0001). Mean overall survival (OS) time was 31.1 months for the TFPI-2-high expressive group and 16.8 months for the TFPI-2- low expressive group.

Figure 3

Expression of CD133 and TFPI-2 protein in cholangiocarcinoma. CD133 was highly expressed (A) but TFPI-2 was negatively expressed (B) in the same cancerous glands in moderately differentiated cholangiocarcinoma. (CD133, TFPI-2 ×400).

Figure 4

Kaplan-Meier survival analysis by CD133 status (n = 218). The y-axis represents the percentage of patients; the x-axis, their survival in months. The green line represents CD133-high expressive patients with a trend of worse survival than the blue line representing CD133- low expressive patients. Mean survival (OS) time was 16.9 months for the CD133- high expressive group and 31.2 months for the CD133- low expressive group (Log rank = 41.642; P = 0.0001).

Figure 5

The inverse correlation between TFPI-2 and CD133. From left to right, expression of TFPI-2 compared with that of CD133 (n = 218) as low to low (1, n = 40), low to high (2, n = 74), high to low (3, n = 63) and high to high (4, n = 41) (r = -0.3876, P = 0.0001).