[Expression of CD82/KAI1 and HIF-1α in non-small cell lung cancer and their relationship to vasculogenic mimicry]

Abstract

Background and objective: Vasculogenic mimicry (VM), found in many high invasive ability tumors, is associated with tumor invasion and metastasis. Many genes exhibit abnormal levels of expression in these tumors. This study aims to find good markers for predicting the invasion and metastasis of non-small cell lung cancer (NSCLC).

Methods: VM and expression of CD82/KAI1 and HIF-1α were examined via immunohistochemistry and histochemistry of 160 NSCLC and 20 normal lung tissue specimens.

Results: In NSCLC, positive rates of 37.5%, 48.8%, and 36.9% were obtained for CD82/KAI1, HIF-1α, and VM, respectively. In normal lung tissue, positive rates of 95.0%, 0, and 0 were obtained for CD82/KAI1, HIF-1α, and VM, respectively. A significant difference was found between the NSCLC and normal lung groups (P<0.01). VM and the expression levels of CD82/KAI1 and HIF-1α were significantly related to tumor differentiation, lymph node metastasis, clinical staging, and postoperative survival time (P<0.01 for all). A negative correlation was found between the expression levels of CD82/KAI1 and HIF-1α; a similar relationship was observed between CD82/KAI1 and VM. A positive relationship between the expression of HIF-1α and VM was revealed; there was a significant relationship between microvessel density (MVD) and the expression of CD82/KAI1 or HIF-1α or VM. VM and overexpression of HIF-1α were related to poor prognosis: the survival rates were significantly lower in positive patients than in negative patients (both P<0.01). The survival rates of the CD82/KAI1-positive and CD82/KAI1-negative groups were significantly different (P<0.01). The five-year survival rate was significantly different between the group with MVD≥22 and the group with MVD<22 (P<0.01). pTNM stage, positive expressions of CD82/KAI1 and HIF-1α, and VM were independent prognostic factors of NSCLC (P<0.01).

Conclusions: VM and the expressions of CD82/KAI1 and HIF-1α in NSCLC are related to differentiation, lymph node metastasis, clinical staging, and prognosis. The combined detection of CD82/KAI1, HIF-1α, and VM has an important role in predicting the progression and prognosis of NSCLC.

1

VM、CD82/KAI1和HIF-1α在NSCLC中的阳性染色以及对照组中的染色。A、B:NSCLC中VM阳性染色(黑箭头所示为VM结构, 红箭头所示为血管, A和B为低分化鳞癌, Elivision^TM×400);C、D、E:NSCLC中CD82/KAI1表达阳性, 主要表达于细胞膜和细胞浆(C为中分化鳞癌, D为低分化鳞癌, E为高分化鳞癌, Elivision^TM×400);F:对照组中CD82/KAI1表达阳性, 主要表达于细胞浆和细胞膜(为正常支气管腺, Elivision^TM×400);G、H、I:NSCLC中HIF-1α表达阳性, 主要表达于细胞核和细胞浆(G为低分化腺癌, H为中分化鳞癌, I为中分化腺癌, Elivision^TM×400);J:对照组中HIF-1α表达阴性(正常肺组织, Elivision^TM×100)。 Positive staining of VM, CD82/KAI1 and HIF-1α in NSCLC and staining in the control group.A, B:positive staining of VM in NSCLC (black arrow is VM, red arrow is vessel, A and B are poor differentiation squamous carcinoma, Elivision^TM×400);C, D, E:positive staining of CD82/KAI1 in membrane and plasma of NSCLC (C is mediate differentiation squamous carcinoma, D is poor differentiation squamous carcinoma, E is well differentiation squamous carcinoma, Elivision^TM×400);F:positive staining of CD82/KAI1 in plasma and membrane of the control group (normal bronchial glands, Elivision^TM×400);G, H, I:positive staining of HIF-1α in nuclei and plasma of NSCLC (G is poor differentiation adenocarcinoma, H is mediate differentiation squamous carcinoma, I is mediate differentiation adenocarcinoma, Elivision^TM×400);J:negative staining of HIF-1α in the control group (J is normal lung tissue, Elivision^TM×100).VM:vasculogenic mimicry; HIF-1α:hypoxia inducible factor-1α; NSCLC:non-small cell lung cancer.

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VM、CD82/KAI1、HIF-1α和MVD阳性组与阴性组NSCLC患者生存曲线。A:VM阳性组与阴性组NSCLC患者生存曲线; B:CD82/KAI1表达阳性组与阴性组NSCLC患者生存曲线; C:HIF-1α表达阳性组与阴性组NSCLC患者生存曲线; D:MVD≥22组与 < 22组NSCLC患者生存曲线。MVD:microvessel density。 Survival curves of NSCLC patients with positive or negative group VM, CD82/KAI1, HIF-1α and MVD.A:survival curves of NSCLC patients with positive or negative VM group; B:survival curves of NSCLC patients with positive or negative CD82/KAI1 expression; C:survival curves of NSCLC patients with positive or negative HIF-1αexpression; D:survival curves of NSCLC patients with MVD≥22 group or < 22 group.