FAP-α and uPA Show Different Expression Patterns in Premalignant and Malignant Esophageal Lesions

Fibroblast activation protein-α (FAP-α) and urokinase-type plasminogen activator (uPA) are serine proteases involved in cancer invasion and metastasis. The authors examined FAP-α and uPA expression in premalignant and malignant stages of esophageal adenocarcinoma by immunohistochemistry. Additionally, Western blotting was performed on fresh-frozen tissue samples. FAP-α and uPA were detected in metaplastic, dysplastic, and carcinoma cells, as well as in adjacent stroma. Stromal FAP-α expression was associated with depth of tumor invasion, while stromal uPA expression correlated with lymph node metastases in adenocarcinomas. Stromal uPA expression in cells with premalignant changes correlated with histological grading. Immunoblotting showed higher protease expression in carcinoma tissues than in normal esophageal epithelium. These results suggest that FAP-α and uPA expression in metaplastic, dysplastic, and esophageal cancer tissue is associated with neoplastic progression of esophageal lesions.     

Invasion by esophageal cancer cells: functional contribution of the urokinase plasminogen activation system, and inhibition by antisense oligonucleotides to urokinase or urokinase receptor

Early metastasis contributes to the very poor prognosis of esophageal carcinoma. The recent immunohistochemical finding that invasive esophageal carcinomas express elevated levels of urokinase (uPA) and urokinase receptor (uPA-R) in vivo suggest that the plasminogen activation system may contribute to metastasis in esophageal cancer. The aim of our study was to functionally investigate, at the molecular level, the relative contribution of uPA and uPA-R to the invasiveness of esophageal cancer cells in vitro. The three esophageal cancer cell lines, OC1-3, generated in our laboratory, were analyzed for uPA and uPA-R expression by RT-PCR, immunoenzymatic staining, and quantitative ELISA. Invasiveness of all cell lines was quantified as percentage cellular invasiveness in a standardized Matrigel in vitro assay. OC1 and OC3, which were found to coexpress both uPA and uPA-R, displayed stronger invasiveness (44% and 32.5% respectively) relative to OC2 (19%) which expressed uPA-R but was negative for uPA. Transfection of OC2 cells with the uPA cDNA resulted in two variants, OC2.uPA1 and OC2.uPA2, stably expressing functional uPA. Both transfectants exhibited enhanced invasiveness (60% and 50% respectively) relative to the parent uPA-negative OC2 cells (19%). Antisense oligonucleotide inhibition of either uPA or uPA-R expression resulted in a similar, marked reduction in invasiveness of esophageal tumor cells which normally coexpress both molecules (OC1, OC3 and the uPA-expressing OC2-transfectant clones). Neither antisense treatment altered the basal invasiveness of OC2, which expresses uPA-R but not uPA. In conclusion, coexpression of uPA with its receptor, uPA-R, is required for functional involvement of the urokinase system in invasion by esophageal carcinoma cells. Our results suggest that these synergistic mediators of invasiveness are quantitatively major contributors to the invasiveness of esophageal carcinoma.     

The correlation of TGF-alpha, EGFR in precancerous lesions and carcinoma of stomach with PCNA expression

OBJECTIVE: To assess the changes and possible role of expression of TGF-alpha and EGFR in gastric carcinogenesis and its relationship with PCNA labelling index (PCNA LI). METHODS: Immunohistochemical study using LSAB kit. RESULTS: (1) The expression of TGF-alpha was increased in normal mucosa and metaplastic tissue near the carcinoma when compared with non-cancer controls (P < 0.01). (2) Increased expression of EGFR was found in the intestinal metaplastic and dysplastic areas compared with nomral mucosa and carcinoma tissue (P < 0.01). (3) Coexpression rate of TGF-alpha and EGFR was higher in dysplasia than in other tissues (P < 0.01). (4) There was a close correlation between the intensities of TGF-alpha, EGFR and PCNA. (5) The expression of TGF-alpha, EGFR and PCNA was not related to infiltration and lymph node metastasis of gastric carcinoma. CONCLUSION: The increased expression of EGFR, TGF-alpha may serve as an important molecular marker of gastric premalignant lesions when combined with measurement of PCNA LI and may be of assistance in screening of early gastric carcinoma in high risk populations.     

胃癌中uPA、PAI-1表达及其与血管生成的关系

目的 观察胃癌组织中uPA、PAI-1mRNA及蛋白的表达，并探讨它们与肿瘤分化、血管生成及临床病理因素之间的关系。方法 用原位杂交及免疫组化S-P法检测110例胃癌组织中uPA、PAI-1的表达，根据CD34阳性的血管内皮细胞计数肿瘤组织微血管密度（MVD）。结果 （1）胃癌组织中uPA mRNA和蛋白、PAI-1 mRNA和蛋白阳性表达定位于胞质；uPA的表达随分化程度的降低有逐渐升高的趋势，PAI-1的表达随分化程度的降低有逐渐降低的趋势。（2）110例uPA mRNA及蛋白表达阳性组MVD值显著高于阴性组，差异均具有显著性（P值均＜0．05）。（3）uPA mRNA及蛋白的表达与临床分期呈正相关（P＜0．05），PAI-1的表达与临床分期和淋巴结转移无相关性。（4）uPA mRNA／蛋白与PAI-1 mRNA／蛋白的表达无相关性。结论uPA与促进胃癌的血管生成密切相关，阻断uPA的分泌和作用途径有望对胃癌浸润转移起抑制作用；胃癌组织中PAI-1可能担当重要的调节剂或者是肿瘤细胞防止自身降解的保护剂而不是这个系统的单纯抑制剂。     

Expression of matrix metalloproteinases in gallbladder carcinoma and their significance in carcinogenesis.

The correlation between matrix metalloproteinase (MMP)-2, MMP-9, and MMP-14 expression on the prognostic parameters of gallbladder carcinoma (GBC) and their role in carcinogenesis were evaluated. Carcinomas of the gallbladder (n=20) and chronic cholecystitis (n=10) were studied for the expression of MMP-2, MMP-9, and MMP-14 by immunohistochemistry. In all of the cases, metaplastic and dysplastic epithelial alterations, and (in GBC histologic type, grade of differentiation, level of infiltration, perineural and angiolymphatic invasion, liver invasion, and lymph node involvement were noted. MMP-2, MMP-9, MMP-14 were expressed in tumor epithelium in 9 (45%), 20 (100%), and 20 (100%) of the cases, respectively. MMP stromal expression including muscle layer, vascular endothelium, fibroblasts, and lymphoid cells were detected in all cases. MMP-2 was not expressed in normal, metaplastic, and dysplastic epithelia. In contrast, MMP-9 and MMP-14 immunoreactivities were present in antral-type metaplastic areas as moderate (grade 2) and strong in dysplastic epithelia (grade 3). Only in mucinous-type GBC was the expression of the MMPs lower than in the other types. No significant correlation was detected with the grade of differentiation, level of infiltration, perineural and angiolymphatic invasion, liver invasion, or lymph node involvement. These data suggest that MMP-9 and MMP-14 overexpression may have an important role in tumorigenesis. MMP-2, MMP-9, and MMP-14 were expressed in GBC epithelium but also the expression in the stromal component may be essential for the malignant potential of GBC.     

Decreased expression of E-cadherin and Yamamoto-Kohama's mode of invasion highly correlates with lymph node metastasis in esophageal squamous cell carcinoma.

OBJECTIVES: A reduction in cell-cell adhesion in cancer cells is an essential step in the progression from localized malignancy to metastatic disease. E-Cadherin is an important component of cell-cell adhesion molecules and may be a crucial determinant of tumor invasion and metastasis. E-Cadherin expression is reported to be correlated with lymph node metastasis in esophageal squamous cell carcinoma (SCC). The objective of this experiment is to examine the factors that are associated with invasion and metastasis of esophageal SCC. METHODS: Forty-six cases of esophageal SCC were examined by immunohistochemical staining for E-cadherin. The relationship between E-cadherin-staining patterns, conventional clinicopathological parameters and Yamamoto-Kohama's (Y-K's) mode of invasion were examined. RESULTS: The expression of E-cadherin on the cell membrane was reduced or lost in some of the esophageal SCC. Lymph node metastasis was highly correlated with the expression pattern of E-cadherin (p = 0.0002) and also highly correlated with Y-K's mode of invasion (p = 0.0078). However, lymph node metastasis was not correlated with any conventional clinicopathological parameters for invasion. CONCLUSIONS: These results indicate that E-cadherin plays a crucial role in invasion and metastasis in esophageal SCC, and that Y-K's mode of invasion highly reflects the invasiveness and metastatic potentials of esophageal SCC cells. Therefore, examination of the expression of E-cadherin and Y-K's mode of invasion would be helpful in predicting lymph node metastasis in esophageal SCC.     

表皮生长因子受体和P53与食管鳞状细胞癌放疗敏感性的关系

目的 分析食管鳞状细胞癌患者标本中表皮生长因子受体(EGFR)和P53表达水平与其临床病理特征的相关性,探讨术前放疗对EGFR和P53表达的影响,为临床食管鳞状细胞癌手术联合放疗的治疗策略提供理论依据.方法 采用免疫组织化学方法检测食管鳞状细胞癌患者标本中EGFR、P53蛋白的表达水平,分析其表达与食管鳞状细胞癌临床病理参数的关系,对比术前放疗对患者癌组织中EGFR和P53表达水平的影响.结果 与正常食管黏膜上皮组织相比,食管鳞状细胞癌组织中EGFR和P53的表达水平均显著升高;食管鳞状细胞癌组织中EGFR和P53的表达均与其组织学分级、浸润程度、有无区域淋巴结转移呈正相关;术前放射治疗可显著降低食管鳞状细胞癌组织中EGFR和P53的表达水平.结论 在食管鳞状细胞癌中,EGFR和P53的表达水平与其临床病理特征有密切关系,且呈正相关,检测两种蛋白的表达水平对食管鳞状细胞癌的恶性程度及预后判断具有重要的临床意义.     

Dysplasia of the gallbladder. Its histogenesis and correlation to gallbladder adenocarcinoma

A total of 50 cases of gallbladder dysplasia found adjacent to carcinoma were examined histologically and immunohistochemically for metaplastic changes in order to elucidate the characteristics of the dysplasia of the gallbladder. The incidence of metaplastic changes in the dysplastic mucosa such as the occurrence of endocrine cells, lysozyme-immunoreactive cells, goblet cells, and Paneth cells were 58%, 74%, 32%, and 22%, respectively. Based on the presence or absence of metaplastic changes, these 50 cases of dysplasia were divided into 40 cases (80%) of metaplastic type dysplasia showing at least one marker of metaplasia and 10 cases (20%) of non-metaplastic type dysplasia showing no metaplasia. On the other hand, these 50 cases of carcinoma were divided into 10 cases of non-metaplastic type carcinoma and 40 cases of metaplastic type carcinoma based on the presence or absence of metaplasia in the tumor tissue. The incidence of metaplastic changes in the dysplastic lesions was compared between the dysplasia adjacent to non-metaplastic type carcinoma and that adjacent to metaplastic type carcinoma. The incidence of metaplasia in the dysplastic mucosa adjacent to metaplastic type carcinoma was higher than that adjacent to non-metaplastic type carcinoma with a statistically significant difference. Moreover, the presence or absence of metaplastic changes was also examined in the surrounding dysplasia and non-tumorous mucosa in each case. Most cases of metaplastic type carcinoma were surrounded by dysplasia with metaplastic changes and by metaplastic epithelium, whereas most cases of non-metaplastic type carcinoma were surrounded by dysplasia without metaplasia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dipeptidyl peptidase IV expression in cancer and stromal cells of human esophageal squamous cell carcinomas,adenocarcinomas and squamous cell carcinoma cell lines

Dipeptidyl peptidase IV (DPPIV) is a transmembrane serine protease which is involved in the process of tumor invasion and development of metastases in human cancers. The aim of this study was to investigate the expression of DPPIV in cancer and stromal cells of both esophageal adenocarcinoma and squamous cell carcinoma (SCC). Tissue material from 159 patients was analyzed using immunohistochemistry. Western blotting was performed on cell lines and fresh frozen tissue sections. Results were compared with clinicopathological features. Evaluation of the immunohistochemical findings revealed significant differences between DPPIV expression in carcinoma cells and stromal cells, depending on the histological tumor type. A significantly higher level of DPPIV was found in adenocarcinomas compared to SCCs while no DPPIV was detected in normal esophageal epithelium. Overexpression of DPPIV in patients with adenocarcinoma was additionally associated with distant metastases. Thus, differences of DPPIV level in esophageal carcinomas compared with normal epithelium showed that esophageal malignancies were associated with an increased amount of cell surface‐bound DPPIV. Radiotherapy in patients had no impact on DPPIV expression in analyzed tissue samples. There was no correlation between DPPIV expression in cancer or stromal cells and survival of the patients.     

Immunohistochemical expression of uPA, uPAR, and PAI-1 in breast carcinoma. Fibroblastic expression has strong associations with tumor pathology

The urokinase-type plasminogen activator (uPA) system has been implicated in tumor spread. We have used immunohistochemistry to examine three components of this system, ie, uPA, uPA receptor (uPAR), and plasminogen activator inhibitor-1 (PAI-1), in a pilot study on 142 cases of breast carcinoma. We wished to determine whether there were any relationships between expression of the proteins in either tumor cells or fibroblasts and clinical and pathological features. Strong uPA expression in each cell type was significantly related to high tumor grade (P = 0.013 and 0.008, respectively), and was more common in invasive than in in situ carcinomas (P < 0.0001). Fibroblastic expression of uPAR was only related to the presence of invasion (P < 0.0001). Strong PAI-1 expression in both cell types was seen in high-grade tumors (tumor cells, P = 0.012; fibroblasts, P < 0.001), but only fibroblastic expression was related to the presence of invasion (P = 0.042). Fibroblastic expression of both uPA and uPAR were positively correlated with tumor size. Although patients with strong fibroblastic expression of uPA showed a tendency toward a shorter time to relapse, none of the plasminogen activator proteins were significantly associated with relapse-free survival. These results suggest that strong expression of uPA, uPAR, and PAI-1 in fibroblasts rather than in tumor cells have the most impact on the clinical behavior of breast cancer. Larger prospective studies are needed to confirm these findings.     

Expression of transforming growth factor-beta1 and transforming growth factor-beta receptors in hepatocellular carcinoma and dysplastic nodules.

In this study we analyzed by immunohistochemistry the expression of TGF-beta1 protein and TGF-beta receptors I and II in 4 low-grade dysplastic nodules, 2 high-grade dysplastic nodules, 6 early, 22 small, and 62 advanced hepatocellular carcinomas. The expression of TGF-beta1 protein by hepatocytes was decreased in advanced hepatocellular carcinoma compared with small or early hepatocellular carcinoma(P < .05). Frequent and intense staining of TGF-beta1 protein was noted in the sinusoidal endothelium of advanced hepatocellular carcinomas despite of its decreased staining in hepatocellular carcinoma cells. Reduced expression of TGF-beta receptors I and II compared with surrounding nontumorous tissue were noted from the early hepatocellular carcinoma stage suggesting that down-regulation of TGF-beta receptors is correlated with progression from premalignant to malignant phenotype. Reduced expression of both TGF-beta1 and TGF-beta receptor II in neoplastic hepatocytes were also significantly correlated with increased tumor size and increased proliferative activity(P < .05). These findings suggest that during hepatocarcinogenesis, the inhibitory effects of TGF-beta1 protein on hepatocellular carcinoma cells is outweighed by its effects on stromal elements, which, overall, contributes indirectly to a tumor growth stimulatory environment. Also, the growth-inhibitory effects of TGF-beta1 may have been further negated by reduced TGF-beta receptors on hepatocellular carcinoma cells.     

Lost expression of AT-rich interaction domain 1A in the gastric mucosa—A constituent of field cancerization in the stomach

Abnormalities of the AT-rich interaction domain 1A (ARID1A) occur in cancer tissues and precursors or premalignant lesions in various organs. To investigate the significance of ARID1A abnormalities in the early phase of cancer development in the stomach, we screened for ARID1A loss and p53 overexpression in glands in non-neoplastic gastric mucosa using immunohistochemistry. We tested 230 tissue blocks of 77 patients with gastric carcinoma, and in 10% of non-neoplastic mucosa we detected ARID1A-lost and in 3.7% p53-overexpressed foci. Loss of ARID1A expression occurred in the scales of several glands, which were morphologically characterized as authentic, pseudo-pyloric, or intestinal metaplastic glands devoid of dysplastic changes. In contrast, p53-overexpressed foci were detected in dysplastic intestinal metaplasia. In early gastric cancer cases (n = 46), ARID1A-lost foci were frequent in samples of patients with Epstein–Barr virus-associated gastric carcinoma (p = 0.037). Ultra-deep DNA sequencing of ARID1A-lost foci revealed frameshift and nonsense mutations in ARID1A. Mapping abnormal glands in the entire resected stomach of the three selected patients demonstrated that ARID1A-lost foci clustered with p53 abnormal glands. ARID1A-lost epithelial cells may develop clonal growth through the pathway, different from p53-abnormal intestinal metaplasia, and require one or more events to develop into an overt carcinoma, such as EBV infection.     

Urokinase plasminogen activator is localized in stromal cells in ductal breast cancer.

Urokinase plasminogen activator (uPA) regulates a proteolytic cascade that facilitates cancer invasion through degradation of the extracellular matrix, and high levels of uPA in human breast cancer tissue correlate with poor prognosis. We previously found that, in ductal breast cancer, uPA mRNA is highly expressed by myofibroblasts surrounding invasively growing cancer cells. However, the localization of uPA protein has not been settled in the published literature. Because uPA is a secreted molecule, it could conceivably be localized differently from its mRNA. We have studied the localization of uPA immunoreactivity in detail. Twenty-five cases of invasive ductal carcinoma were analyzed with three different uPA antibody preparations, all of which gave an essentially identical stromal staining pattern. Using double immunofluorescence, we identified uPA immunoreactivity in myofibroblasts and macrophages in all cases examined. Additionally, in approximately half of the tumors, we saw uPA staining of endothelial cells. In 3 of the 25 cases, a small subpopulation of the cancer cells was uPA-positive. We conclude that uPA immunoreactivity is almost exclusively associated with stromal cells, which thus play a major role in generation of proteolytic activity in ductal breast cancer.     

Expression of p53 in human esophageal carcinoma: an immunohistochemical study with correlation to proliferating cell nuclear antigen expression.

Immunolocalization of the nuclear protein p53 tumor suppressor gene product is considered to be one of the best methods of detecting a mutated form of p53. We have studied p53 immunohistochemically by using monoclonal antibody pAb1801 in 15 cases of esophageal squamous cell carcinoma. Immunoreactive p53 was observed in the nuclei of tumor cells in 4% paraformaldehyde-fixed, frozen sections (12 of 15) and paraffin-embedded sections (11 of 15), but not in routinely processed (10% formalin-fixed) specimens. p53 expression was closely correlated with the malignant phenotype, including dysplasia. p53 was not observed in histologically normal mucosa, except in three cases in which scattered immunoreactivity was observed in parabasal and basal cells. Immunostaining of ki67 and proliferating cellular nuclear antigen on adjacent tissue sections revealed that p53 expression was strongly correlated with ki67 and proliferating cellular nuclear antigen in carcinoma and dysplastic cells, but not in normal mucosa, suggesting involvement of the mutated form of p53 in the cell cycle of malignant cells. Immunohistochemical patterns of p53 were not related significantly to clinicopathologic parameters in the cases examined. Therefore, p53 expression was strongly associated with the proliferation of carcinoma cells but not with that of normal cells in esophageal carcinoma.     

Differentiation between metaplastic carcinomas and sarcomas of the human female breast by fibronectin

Summary The distribution pattern of fibronectin in metaplastic carcinomas, stromal sarcomas, malignant cystosarcoma phyllodes tumours and histiocytic type lymphomas of the human female breast has been studied using the indirect immunoperoxidase technique on formalin fixed paraffin embedded tissue.Fibronectin was demonstrated as intensely stained strands between tumour cells forming an irregular network in metaplastic carcinomas and lymphomas. Stromal sarcomas and the malignant stromal component of the phyllodes tumours exhibited, in contrast, a uniform staining throughout tumour cells and stroma which was weaker than in adjacent normal-looking connective tissue.We suggest that the intense staining reaction of metaplastic carcinomas is due to the scirrhous reaction generally associated with invasive human breast carcinomas. The advantage of using fibronectin as a diagnostic tool in the differentiation of carcinoma/lymphoma versus sarcoma is the fact that the antigen is a stromal marker and its staining intensity is not influenced by the morphology or degree of differentiation of non-mesenchymal tumours.     

Modulation of urokinase and urokinase receptor gene expression in human renal cell carcinoma.

In vivo and in vitro experimental models have suggested a major role for the urokinase-type plasminogen activator (uPA) in tumor cell invasion and metastasis. The uPA proteolytic activity of tumor cells has been shown to be largely determined by the extent of the expression and saturation of the uPA receptor. We have analyzed the expression and cellular localization of both uPA and uPA receptor at the protein and mRNA levels in 33 paired samples of renal cell carcinoma (RCC) and non-tumorous kidney tissue. In comparison with adjacent normal non-tumorous kidney tissues RCC tumor cells modestly overexpressed uPA-receptor mRNA and showed significantly decreased uPA mRNA expression. However, the immunoreactive uPA content of tumor cells was comparable to that of the surrounding normal non-tumorous kidney tissue. Assuming constancy of the uPA-receptor affinity for uPA this indicates that a proportion of the RCC-associated uPA may be derived from an exogenous source and subsequently concentrated at the tumor cell surface via uPA receptor expression. The modest increase in uPA receptor expression may lead to a normalization of uPA antigen content in RCC; however, it is not sufficient to substantially increase tumor tissue-uPA content over the level of normal non-tumorous kidney tissue.     

Loss of Retinoic Acid Receptor-β Expression Is an Early Event during Esophageal Carcinogenesis

We recently observed that growth inhibition of esophageal cancer cells by retinoic acid (RA) was associated with both constitutive expression and RA-induced up-regulation of RA receptor beta (RAR-beta). Cell lines that did not express RAR-beta were also resistant to RA. To explore the expression of RAR-beta mRNA in vivo, we analyzed esophageal tissue specimens from 16 normal mucosae, 30 dysplastic lesions, and 157 esophageal tumors by in situ hybridization. RAR-beta was detected in 88% (14/16) of normal esophageal tissues and in 96% (96/100) of distant normal esophageal mucosa from cancer specimens. In contrast, RAR-beta was expressed in only 57% (17/30) of dysplastic lesions and in 54% (84/157) of carcinomas. Among esophageal carcinomas RAR-beta mRNA was expressed in 62% (26/42) of well-differentiated, 54% (27/50) of moderately differentiated, and only 29% (4/14) of poorly differentiated SCCs. Our data suggest that the loss of RAR-beta expression is an early event associated with esophageal carcinogenesis and the status of squamous differentiation.     

Basal-cell keratins in cervical reserve cells and a comparison to their expression in cervical intraepithelial neoplasia.

Expression of keratins 5, 14 and 17 in endocervical subcolumnar reserve cells was detected by means of immunohistochemical studies using polypeptide specific monoclonal antibodies. These particular keratins that were found among others in basal cells could also be detected to a variable extent in metaplastic and dysplastic cervical lesions. In some cases of immature squamous metaplasia all three keratin subtypes were expressed throughout the full thickness of the epithelium. In contrast, in mature squamous metaplasia a compartmentalization of these keratins was observed. Mature squamous metaplastic epithelium showed a keratin distribution pattern comparable to ectocervical squamous epithelium, with the exception of keratin 17, which was only sporadically found in the basal layer of ectocervical epithelium and was always present in the basal cells of mature squamous metaplastic epithelium. During progression of cervical intraepithelial neoplasia a clear increase in the expression of keratin 17 was observed. However, also keratins 5 and 14 were expressed. Our results demonstrate that a considerable number of premalignant lesions of the uterine cervix express the same keratins as found in the progenitor reserve cells. Lesions that lack expression of keratin 17 may form a distinct group, which are regressive in nature and do not progress into cervical cancer.     

胃癌组织中尿激酶型纤溶酶原激活剂及其受体基因表达和临床意义

目的：研究尿激酶型纤溶酶原激活剂（ｕＰＡ）及其特异受体（ｕＰＡＲ）与胃癌的关系及其在胃癌浸润转移中的作用。方法：采用ｃＤＮＡ－ｍＲＡＮ原位分子杂交技术,分别检测了６４例胃癌及其癌旁组织中ｕＰＡ和ｕＰＡＲｍＲＮＡ表达情况,同时结合病人的临床生物学指征进行分析。结果：癌与癌周比较,ｕＰＡ和ｕＰＡＲｍＲＮＡ阳性表达率明显升高,Ｐ〈０．００１。在伴有淋巴结转移的病例中,ｕＰＡ和ｕＰＡＲ阳性例数分别为１９／２９和２４／２９,与无转移的１０／３５和１３／３５相比,Ｐ分别〈０．０１和〈０．００１。在浸润到肌层、浆膜层的病例中ｕＰＡ和ｕＰＡＲ阳性例数分别为２５／３８和３０／３８,与浸润到粘膜和粘膜下层的４／２６例和７／２６相比,Ｐ均〈０．００１。在ｕＰＡ和ｕＰＡＲ同时阳性的病例中,伴有淋巴结转移和浸润到肌层以下的分别占１５／２