Influence of intratumoral basic fibroblast growth factor concentration on survival in ovarian cancer patients

Since basic fibroblast growth factor (bFGF) is considered as a potent mitogen that stimulates the growth of ovarian cancer cells, we evaluated the role of bFGF as a prognostic marker in patients with epithelial ovarian cancer. bFGF was quantified from the tumor cytoplasm of 76 patients with FIGO stage I–III ovarian cancer by a human FGF basic immunoassay (R&D Systems). After a mean follow-up period of 42 months, 50 patients were found to be free of tumor while 26 patients had died of the disease. The median bFGF concentration was 352.9 pg/mg (range 27.4–26 600 pg/mg). After dichotomization cytoplasmic expression of bFGF was found to be low in 44 tumors (≤500 pg/mg) and high in 32 tumors (>500 pg/mg). The probability of overall survival was 38.8 and 58.5% in the low bFGF and high bFGF groups, respectively (log-rank P=0.0066). In multivariate analysis, residual tumor after initial surgery and bFGF, but not histologic grade or stage of the disease, independently influenced the overall survival probability. Furthermore, tumors with high cytoplasmic expression of bFGF revealed a much greater stromal content. Therefore, we hypothesize that bFGF may induce a fibroblastic response which causes tumors with a high bFGF to be less aggressive than those with less stromal tissue.     

Co-expression of hepatocyte growth factor and c-Met predicts peritoneal dissemination established by autocrine hepatocyte growth factor/c-Met signaling in gastric cancer

Epithelial-mesenchymal transition (EMT) promotes and facilitates migration and invasion of epithelial tumor cells. EMT is induced by factors such as hepatocyte growth factor (HGF). This study aimed to establish whether the HGF/c-Met pathway is associated with gastric cancer metastasis; especially peritoneal dissemination. HGF and c-Met expression and EMT-related molecules were evaluated using real-time PCR and immunohistochemistry. The role of the HGF/c-Met pathway in EMT and anoikis was determined, and kinase inhibitor SU11274 was tested for its ability to block HGF-induced biological effects. In HGF(-) /c-Met(+) gastric cancer cells, recombinant HGF promoted an EMT phenotype that was characterized by morphology, impaired E-cadherin and induction of vimentin. HGF promoted cell growth, invasiveness and migration and inhibition of anoikis. SU11274 blocked HGF-induced EMT and biological effects in vitro. In HGF(+) /c-Met(+) gastric cancer cells, HGF did not affect the biological outcome of EMT and anoikis, but SU11274 exerted the same inhibitory effects as in HGF(-) /c-Met(+) cells. In vivo, HGF(+) /c-Met(+) gastric cancer cells only established peritoneal dissemination and SU11274 inhibited tumor growth. Clinically, HGF expression was significantly correlated with c-Met expression in gastric cancer. Increased HGF and c-Met had a significant association with poor prognosis and predicted peritoneal dissemination. We demonstrated that the HGF/c-Met pathway induces EMT and inhibition of anoikis in gastric cancer cells. Co-expression of HGF and c-Met has the potential to promote peritoneal dissemination in gastric cancer. Blockade of the autocrine HGF/c-Met pathway could be clinically useful for the treatment of peritoneal dissemination in gastric cancer.     

Targeting fibroblast growth factor pathways in endometrial cancer

Novel treatments that improve outcomes for patients with recurrent or metastatic endometrial cancer (EC) remain an unmet need. Aberrant signaling by fibroblast growth factors (FGFs) and FGF receptors (FGFRs) has been implicated in several human cancers. Activating mutations in FGFR2 have been found in up to 16% of ECs, suggesting an opportunity for targeted therapy. This review summarizes the role of the FGF pathway in angiogenesis and EC, and provides an overview of FGFR-targeted therapies under clinical development for the treatment of EC.     

Epidermal growth factor receptor and insulinlike growth factor 1 receptor expression predict poor survival in pancreatic ductal adenocarcinoma

BACKGROUND:

The aim of this study was to evaluate the expression of epidermal growth factor receptor (EGFR) and insulinlike growth factor 1 receptor (IGF‐1R) proteins and IGF‐1R gene copy numbers in pancreatic ductal adenocarcinoma in relation to patients' characteristics and prognosis.

METHODS:

Immunohistochemical staining was performed on formalin‐fixed paraffin‐embedded tissue derived from tumor specimens recovered during surgery. Slides were evaluated for membranous EGFR and IGF‐1R staining using both the HercepTest and the semiquantitative H‐score systems. Chromogenic in situ hybridization was performed to quantify IGF‐1R gene copy number. The primary outcome was the association between EGFR expression, IGF‐1R expression—in both neoplastic epithelial and stromal cells—or IGF‐1R gene copy number and overall survival. Secondary outcomes included associations between EFGR and IGF‐1R expression and pathologic variables.

RESULTS:

A total of 105 patients were included. EGFR expression was present in 30.4% of cases and was associated with lymph node metastasis (P = .038). IGF‐1R was overexpressed in 53% of tumors and correlated with higher tumor grade (P = .033). High membranous expression of EGFR (P < .001) and/or IGF‐1R (P = .004), the cytoplasmic detection of EGFR (P = .027), and high expression levels of IGF‐1R in the tumoral stroma (P < .001) were all associated with shorter overall survival, being significantly better in patients who simultaneously do not express membranous EGFR or stromal IGF‐1R.

CONCLUSIONS:

EGFR and IGF‐1R expression, in neoplastic and stromal cells, seems to be an important prognostic factor. Cancer 2012;3484–3493. © 2011 American Cancer Society.     

Determination of epidermal growth factor receptor provides additional prognostic information to measuring tumor angiogenesis in breast carcinoma patients

Summary Recent studies have shown that women with invasive breast carcinoma having high microvessel density (MVD) (a measure of tumor angiogenesis) or epidermal growth factor receptor (EGFR) expression have increased risk for metastasis and/or decreased survival. To determine if MVD and EGFR expression provide additive prognostic information, we analyzed these two prognostic indicators in the primary invasive breast carcinomas from 165 consecutive patients, who were followed for a median of 51 months. Univariate analysis showed a highly significant (p<0.001) association of MVD with overall and relapse-free survival in all patients, including both node-negative and node-positive groups (see JNCI 84:1875–1887, 1992). For EGFR, although univariate analysis suggested that women with tumors showing EGFR expression relapsed earlier and, perhaps, died earlier, the differences were not statistically significant. Multivariate analysis, in contrast, revealed that determination of EGFR did provide significant additional information to that already provided by MVD for predicting relapse-free survival in all women (p=0.001) and in the subset of node-positive women (p=0.007). Among node-negative women, however, the contribution of EGFR expression in predicting relapse-free survival was not significant (p=0.12). Likewise, EGFR measurement did not provide significant additional information beyond that of MVD alone for predicting overall survival. Thus, EGFR provides additional prognostic information to determination of MVD, but only for relapse-free survival in node-positive women with invasive breast carcinoma.     

Tumor ploidy as a risk factor for disease recurrence and short survival in surgically-treated dukes' B2 colon cancer patients

The risk factors for colon cancer recurrence following a curative intent surgery include the presence of metastatic disease, the tumor location and size, number of positive lymph nodes, the presence of adhesions, perforation, bowel obstruction, depth of invasion, histological grade, percentage of S-phase content, and cell kinetic profile. The DNA content of colon cancers in 20 Dukes' B2 patients in follow-up evaluation at our center, who relapsed, either locally or systemically following surgical treatment was measured by image analysis. The data were pair-matched for age, sex, tumor site, and grade with 20 Dukes' B2 patients who had no evidence of disease. Aneuploidy occurred in 16 (80%) patients with recurrence, as compared with only in 8 (40%) in the control group. Aneuploidy was associated with significantly higher tumor recurrence rate (P = 0.024) and shorter overall survival (P 0.002). Our data may point out a possible indication for systemic adjuvant chemotherapy in Dukes' B2 colon cancer patients who have aneuploid tumors on image analysis. This warrants further investigation in a prospective controlled randomized study.     

脑膜瘤组织中bFGF及FGFR-1蛋白表达的研究

目的　探讨碱性成纤维生长因子 (basicfibroblastgrowthfactor ,bFGF)及成纤维生长因子受体 1(fibroblastgrowthfactorreceptor 1,FGFR 1)在脑膜瘤中的表达及其与脑膜瘤组织病理学和复发的关系。方法　用免疫组化技术检测bFGF、FGFR 1在不同类型的脑膜瘤组织中的蛋白表达 ,用组织病理学判断脑膜瘤的良恶性。结果　脑膜瘤细胞有不同程度的bFGF及FGFR 1表达 ,其表达阳性率与肿瘤的良恶性和复发有关。结论　bFGF和FGFR具有促进脑膜瘤细胞的增殖和生长的作用。脑膜瘤表达bFGF、FGFR的阳性率可作为鉴别肿瘤良恶性的有用指标 ,并对脑膜瘤的预后和术后复发起提示作用。     

卵巢上皮性癌组织中PTTG的表达与微血管密度和bFGF的关系

目的:探讨垂体肿瘤转化基因(PTTG)在卵巢上皮性癌组织中的表达及其与微血管密度(MVD)计数和碱性成纤维细胞生长因子(bFGF)蛋白表达的关系。方法:采用逆转录聚合酶链反应(RTPCR)技术,检测42例卵巢上皮性癌组织中PTTGmRNA的表达;应用免疫组织化学法,检测PTTG和bFGF蛋白的表达,CD34标记血管内皮细胞并计数MVD。以18例卵巢良性上皮性肿瘤和12例正常卵巢组织进行对照。结果:卵巢上皮性癌组织中PTTG高度表达,并与手术病理分期和淋巴结转移正相关,P值均<0.05;PTTG的表达与年龄、病理类型或组织学分级无关,P>0.05。卵巢上皮性癌组织中PTTG的表达与bFGF蛋白表达及微血管密度正相关,P值均<0.05。结论:卵巢上皮性癌组织中PTTG高度表达参与了卵巢上皮性癌的发生及演进过程。PTTG可能通过激活bFGF蛋白表达促进新生血管生成而促使卵巢上皮性癌发生转移。     

Serum levels of angiogenin,basic fibroblast growth factor and endostatin in patients receiving intensive chemotherapy for acute myelogenous leukemia

Angiogenesis seems to be important both in the pathogenesis of acute myelogenous leukemia (AML) and for the susceptibility of AML blasts to chemotherapy. Recent clinical studies even suggest that antiangiogenic therapy can induce disease control in patients with AML relapse. In this context we have investigated the profile of the systemic component of angiogenic regulation in AML by characterizing the serum levels of (i) the angiogenic regulators angiogenin, basic fibroblast growth factor (bFGF) and endostatin; (ii) the endothelial cell marker soluble (s) E-selectin. Patients with untreated AML had increased levels of angiogenin, endostatin and sE-selectin, whereas the levels of bFGF were not significantly altered. The systemic levels of the proangiogenic bFGF, the antiangiogenic endostatin and the endothelial cell marker sE-selectin showed significant correlations, whereas angiogenin and sE-selectin levels were not correlated. Furthermore, intensive chemotherapy resulted in decreased systemic levels of the 2 proangiogenic mediators angiogenin and bFGF, whereas endostatin levels remained high after treatment. Although angiogenin normally is a part of the acute phase reaction, its systemic levels were not altered when patients with chemotherapy-induced cytopenia developed complicating bacterial infections. Our results suggest that intensive chemotherapy can modulate the systemic component of angiogenic regulation in AML patients.     

膀胱癌中bFGF和血管形成的研究

目的：探讨碱性成纤维细胞生长因子（ｂＦＧＦ）和血管形成与膀胱癌的发病及生物学行为之间关系。方法：采用免疫组化方法检测７２例膀胱癌组织和２１例正常膀胱组织中ｂＦＧＦ和第ＶＩＩＩ因子相关抗原表达。结果：膀胱癌组织中ｂＦＧＦ表达和微血管密度（ＭＶＤ）均显高于正常膀胱胱组织，而且两与肿瘤病理分级分期均密切相关。肿瘤复发的ｂＦＧＦ表达和ＭＶＤ均显高于复发，ｂＦＧＦ强阳性表达的ＭＶＤ值显高于阴性及弱阳性表达，结论：ｂＦＧＦ通过促进血管形成而在膀胱癌的发生发展过程中起着重要的作用，而且ｂＦＧＦ和ＭＶＤ可作为膀胱癌生物行为和预后的评估指标。     

Subcellular localization of basic fibroblast growth factor and fibroblast growth factor receptor 1 in pituitary adenomas

The aim of this study was to assess the subcellular localization of basic fibroblast growth factor (bFGF) and fibroblast growth factor receptor 1 (FGFR1) in pituitary adenomas. We studied 61 patients who had primary pituitary adenomas and underwent operation. The immunohistochemistry for bFGF, FGFR1, and MIB-1 was examined in paraffin-embedded tissues. The bFGF immunoreactivity in the nucleus was recorded as the bFGF nuclear index, which was calculated as the percentage of tumor cells with the bFGF immunoreactivity in the nuclei when more than 1000 tumor cells were examined. Recurrent adenomas were found in 7 patients during follow-up periods ranging from 8 to 134 months (mean, 57.2). The recurrent adenomas had significantly larger mean bFGF nuclear indices (74.8±28.8%) than the nonrecurrent adenomas (25.4±32.1%,P=0.0003). The bFGF nuclear index also correlated significantly with the maximum tumor diameters and the invasiveness to the cavernous sinuses (Knosp grade) in the adenomas. The cytoplasmic FGFR1 immunoreactivity was inversely correlated (P<0.02) with maximum tumor diameter. Neither cytoplasmic bFGF, cytoplasmic FGFR1, nor MIB-1 staining index showed any relationship with the recurrence of pituitary adenomas. These findings suggest that the nuclear accumulation of bFGF plays an important role in the progression of pituitary adenomas without its receptors.     

Population-based survival analysis of colorectal cancer patients in Singapore, 1968-1992

Since the 1980s, colorectal cancer incidence in Singapore has ranked second to lung in males and females. We describe a population-based analysis of survival of colorectal cancer patients diagnosed from 1968 to 1992 in Singapore. Data of colorectal cancer patients diagnosed during 1968-1992 were retrieved from the Singapore Cancer Registry. Patients were passively followed up for death to the end of 1997. The final dataset consisted of 10,114 subjects. Observed and relative survival rates were calculated by stage (localized, regional metastases and distant metastases), age, ethnicity and calendar period for both genders. Over the study period, a significant progress in survival of colorectal cancer patients was observed. For localized cancer of the colon, the 5-year age-standardized relative survival (ASRS) increased from 36% in 1968-1972 to 66% in 1988-1992 for males and from 32 to 71% for females. For localized rectal cancer, the 5-year ASRS improved from 25 to 66% for males and from 23 to 66% in females. Similarly, improvement was observed in colorectal cancer patients with regional metastases, but not in those with distant metastases. Calendar year period and clinical stage of disease were identified as major significant prognostic factors of survival for colorectal cancer. The substantially improved colorectal cancer survival rates reflected the interplay of cancer control activities in various areas, such as health promotion, early diagnosis and treatment. Our study shows a unique changing pattern of survival experience for colorectal patients from a country undergoing rapid economic development.     

绝经前后子宫内膜癌生存因素分析

目的:探讨绝经前后子宫内膜癌的临床资料及预后相关因素。方法:选取2008年1月至2012年3月在唐山市妇幼保健院诊断为子宫内膜腺癌,并接受了手术方法治疗的患者240例。随访共36个月,至2015年3月,分为绝经前和绝经后两组。绝经前115例,绝经后125例,比较两组患者的临床特征、单因素分析两组影响子宫内膜癌患者的预后相关因素及两组间生存率差异。结果:本研究显示绝经前组和绝经后组子宫内膜癌在腺癌类型、深肌层浸润、宫颈受累、淋巴转移、附件受累、病理分级例数、ER、PR阳性例数,比较两者均差异无显著性(P＞0.05)。两组患者的组织类型、浸润深度、病理分级、附件转移、宫颈受累是影响子宫内膜癌预后的独立因素。绝经前与绝经后患者的3年生存率分别为87%、72%,P＜0.05,有明显统计学意义。结论:绝经前后子宫内膜癌预后差异显著,绝经是预后的独立因素。     

Expression of hepatocyte growth factor and its receptor c-Met in human pituitary adenomas

Hepatocyte growth factor (HGF) and its receptor c-Met have been known as key determinants of growth and angiogenesis in some brain tumors like gliomas, meningiomas, and schwannomas. But little is known about their expression in pituitary adenomas. In this study, the expression of HGF and c-Met in pituitary adenomas of different histology types was investigated by immunohistochemistry, and correlative analysis of their expression with microvessel density (MVD), Ki-67 expression, and other clinicopathologic factors was made. The results showed that the expression of HGF and c-Met exists in 98% (64 of 65) and 92% (60 of 65) pituitary adenomas, respectively, and co-expression of them existed in 91% (59 of 65) adenomas. HGF had significant correlation with MVD (Spearman''s correlation coefficient, r = .31, P = .01) and Ki-67 (r = .32, P = .01). c-Met had significant correlation with MVD (r = .30, P = .02) and Ki-67 (r = .38, P = .00). HGF and c-Met expression had no significant correlation with age or extrasellar extension. There were no significant differences in HGF and c-Met expression between pituitary adenomas of different histology types. The results indicate that HGF and c-Met are widely expressed in pituitary adenomas, and their expression correlates with MVD and Ki-67 expression.     

Human chondrosarcoma secretes vascular endothelial growth factor to induce tumor angiogenesis and stores basic fibroblast growth factor for regulation of its own growth.

Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are well-known factors that induce neovascularization in many tumors. The molecular mechanisms that regulate tumor angiogenesis in human chondrosarcoma are not clear. We assessed in this work the angiogenic activities of a human chondrosarcoma cell line (OUMS-27) in vivo and determined the efficacies of angiogenic factors derived from OUMS-27 cells on human umbilical vein endothelial cells (HUVECs) in vitro. Tumor xenografts induced an increase in the formation of neovessels, but the distributions of Ki-67 antigen, VEGF and bFGF were unaffected. We also demonstrated that OUMS-27 cells secreted VEGF(165) into the culture medium and that it was the maximal angiogenic factor to stimulate endothelial proliferation and migration in chondrosarcoma. Anti-VEGF antibodies induced an approximately 70% inhibition of these responses of HUVECs, but did not have any effect on OUMS-27 cells. Anti-bFGF antibodies suppressed not only the activities of HUVECs but also the growth of tumor cells in vitro. We indicate that angiogenesis is principally elicited by VEGF(165) and that tumorigenesis is mainly regulated by bFGF stored in the extracellular matrix of OUMS-27 cells. The present study may offer the availability of combination therapies for inhibition of VEGF and bFGF action on vascular endothelial cells and chondrosarcoma cells, respectively.     

沙利度胺对人肾癌细胞增生及碱性成纤维细胞生长因子表达的影响

目的观察沙利度胺对人肾癌细胞株786—0增生及碱性成纤维细胞生长因子（bFGF）表达的影响。方法将细胞分成沙利度胺6．25、25、100ug／ml组及对照组；应用MTT方法测定细胞抑制率；半定量RT-PCR和流式细胞术分别从mRNA和蛋白水平观察沙利度胺对786—0细胞bFGF表达的作用。结果沙利度胺在6．25～100ug／ml范围内能明显抑制786—0细胞增生，作用48、72h，IC50分别为46．42、19．56ug／ml。凋亡率从12．43％增加到30．30％，并伴随bFGF表达水平下降，以25ug/ml对bFGF抑制最显著。结论沙利度胺能抑制肾癌细胞bFGF的表达，促进凋亡，抑制细胞增生。     

Upregulation of basic fibroblast growth factor in breast carcinoma and its relationship to vascular density, oestrogen receptor, epidermal growth factor receptor and survival

Background: Angiogenesis, the process whereby endothelial cells divide and migrate to form new blood capillaries, has been assessed in tumours by measuring microvessel density. High microvessel density is a significant adverse prognostic factor in breast cancer. The angiogenic factor, basic fibroblast growth factor (bFGF), has been associated with tumourigenesis and metastasis in several human cancers. There are few quantitative studies of bFGF expression in normal tissues compared to cancer.Patients and methods: We have measured bFGF levels in 149 human primary breast carcinomas and assessed the findings in relation to microvessel density, oestrogen receptor (ER) and epidermal growth factor receptor (EGFR).Basic FGF levels were measured by ELISA. Western blotting and immunohistochemistry were carreid out to confirm the presence of bFGF.Results: Levels of bFGF were more than 10-fold higher in tumour cytosols compared to reduction mammoplasty tissue and 3-fold compared to non neoplastic cytosols from the same breast as the tumour (P < 0.0001). Immunohistochemistry showed bFGF protein was localised exclusively in the stroma whereas no bFGF staining was observed in the epithelial cells. High bFGF levels were significantly related to high ER (P = 0.01). Similarly, high bFGF levels were significantly related to low grade (P = 0.046) and to small tumour size (P = 0.04). No significant relationship was observed between bFGF and microvessel count, EGFR or age. In univariate analysis and in a Cox proportional hazard model bFGF did not reach significance for overall or relapse free survival.Conclusions: Our results show that although bFGF is elevated in breast carcinomas compared to normal breast tissue it is not related to microvessel density and it is not an independent predictor of survival in breast cancer patients. Basic FGF may be one of multiple factors that synergise with other growth factors such as VEGF to enhance angiogenesis.     

血清VEGF、bFGF与胃癌生物学行为的关系

目的:探讨VEGF、bFGF与胃癌的生物学行为的关系,复发转移患者血清VEGF、bFGF的表达水平与化疗疗效的关系。方法:应用ABC-ELISA方法检测胃癌患者血清VEGF、bFGF的表达情况。结果:(1)术前未作放化疗的胃癌组患者术前血清VEGF、bFGF表达水平明显高于健康体检者(P<0.05),也明显高于同组患者术后血清VEGF、bFGF表达水平(P<0.05)。(2)术前未作放化疗的胃癌组患者术前血清VEGF、bFGF的表达水平与原发肿瘤的浸润深度、TNM分期、淋巴结转移、远处转移有关。(3)术前未作放化疗的胃癌组患者术前血清VEGF与bFGF的表达水平呈正相关(r=0.439,P<0.01)。(4)胃癌患者复发转移组化疗前血清VEGF、bFGF的表达水平比健康体检者及无病生存组明显增高(P<0.05)。(5)胃癌患者复发转移组化疗后CR PR组血清VEGF、bFGF表达水平比化疗前明显减低(P<0.05),胃癌患者复发转移组化疗后NC PD组血清VEGF、bFGF表达水平比化疗前略高,但没有显著性差异(P>0.05),胃癌患者复发转移组化疗后CR PR组血清VEGF、bFGF表达水平比NC PD组明显低(P<0.05)。结论:胃癌患者血清VEGF、bFGF与胃癌生物学行为有关,而且与胃癌化疗疗效有关。血清VEGF、bFGF可能成为胃癌的诊断、术后随访、复发转移监测新的肿瘤标志物。     

胃癌组织中H.pylori感染与bFGF蛋白表达关系及其临床意义

目的 :探讨幽门螺旋杆菌感染(Helicobacterpylori,H .pylori)与碱性成纤维细胞生长因子 (basicfibroblastgrowthfac tor ,bFGF)蛋白表达的关系及其与胃癌发生和发展的关系。方法 :应用免疫组化方法检测了 63例胃癌存档标本和 10例正常胃组织中bFGF的蛋白表达。结果 :63例胃癌存档蜡块中有 45例阳性 ,Hp阳性胃癌组和转移性胃癌组显著高于Hp阴性胃癌组和非转移性胃癌组 ,P <0 0 1。阳性着色定位于肿瘤细胞、血管内皮细胞及肿瘤基质。结论 :H .pylori感染增强了bFGF的表达 ,bFGF可能通过自分泌和旁分泌机制诱导胃癌血管生成 ,或通过胞内分泌作用刺激某些酶的产生 ,从而促进肿瘤的浸润。     

The tumour-stromal interaction between intratumoral c-Met and stromal hepatocyte growth factor associated with tumour growth and prognosis in non-small-cell lung cancer patients

Immunohistochemical analyses of the effects of hepatocyte growth factor (HGF) and c-Met expression on tumour growth and angiogenesis were performed on 88 patients with non-small-cell lung cancers (NSCLCs). In all, 22 carcinomas (25.0%) were intratumoral HGF-positive, 14 carcinomas (15.9%) were stromal HGF-positive, and 36 carcinomas (40.9%) were intratumoral c-Met-positive. None of the carcinomas were stromal c-Met-positive. Examination of tumour growth revealed that the frequency of tumours with a high Ki-67 index was significantly greater for stromal HGF-positive tumours than for stromal HGF-negative tumours (P=0.0197). The frequency of tumours with a high Ki-67 index was also significantly greater for intratumoral c-Met-positive tumours than for intratumoral c-Met-negative tumours (P=0.0301). However, there was no significant difference in tumour vascularity with relation to intratumoral HGF status, stromal HGF status, and intratumoral c-Met status. The survival rate of patients with intratumoral c-Met-positive tumours was significantly lower than for patients with c-Met-negative tumours (P=0.0095). Furthermore, the survival rate of patients with both intratumoral c-Met-positive and stromal HGF-positive tumours was significantly lower than for patients with either positive tumours, and that of patients with both negative tumours (P=0.0183 and P=0.0011, respectively). A univariate analysis revealed that intratumoral c-Met expression was a significant prognostic factor of NSCLC patients (relative risk=2.642, P=0.0029). The present study demonstrates that tumour-stromal interaction between tumour cell-derived c-Met and stromal cell-derived HGF affects tumour growth and the prognosis of NSCLC patients.