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1.
The prognostic influence of blood-vessel invasion (BVI), lymphatic-vessel invasion (LVI) and neural invasion (NI) was evaluated retrospectively in a series of 161 patients with squamous cell carcinoma (SCC) of the esophagus who underwent esophageal resection. Evidence of BVI, LVI and NI was found in 32.9%, 48.5% and 26.1%, respectively. Incidence of BVI, LVI and NI was significantly higher in high pT categories (pT3 and pT4) than in low pT categories (pTI and pT2) and in patients with distant metastases than in patients without distant metastases. Incidence of LVI and NI in lymph-node-positive patients was significantly higher than in lymph-node-negative patients. The 5-year survival rate was significantly lower in patients with BVI or LVI than in patients without BVI or LVI. Patients with evidence of NI showed no significant differences in 5-year survival from patients without evidence of NI. By stepwise multivariate Cox regression analysis, BVI and LVI were shown to be independent prognostic factors. A search for vascular invasion may therefore provide additional prognostic precision in SCC of the esophagus. © 1995 Wiley-Liss, Inc.  相似文献   

2.
The prognostic significance of blood-vessel invasion (BVI) and lymphatic-vessel invasion (LVI) was evaluated in a retrospective series of 529 gastric-cancer patients who underwent potentially curative surgery. Evidence for BVI was found in 127 patients (24.0%), while LVI was demonstrated in 245 patients (46.3%). The incidence of both BVI and LVI run parallel to increasing tumor size and tumor stage as well as to decreasing grade of tumor differentiation. The incidence of BVI and LVI was higher in lymph-node-positive patients than in lymph-node-negative patients. The 5-year-survival rate was significantly lower (p less than 0.0001) in patients with BVI or LVI (14.9% and 22.2% respectively) than in patients without BVI or LVI (54.7% and 64.1% respectively). Both BVI and LVI were shown to be prognostic factors independent of tumor stage, grade of differentiation or lymph-node involvement. In a multivariate Cox regression analysis, the gain of prognostic information provided by the evidence of BVI and LVI was shown to exceed the information obtained by the combination of tumor stage, grade of differentiation and lymph-node involvement. A careful search for vascular invasion in gastric cancer may therefore provide additional useful information for identifying patients who are at high risk and who may be candidates for adjuvant therapy in future clinical trials.  相似文献   

3.
BACKGROUND AND OBJECTIVES: Growth and metastasis of malignant tumors depend on the angiogenesis. The aim of this study was to elucidate the prognostic significance of angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) expression in advanced colorectal carcinoma. METHODS: Totally, 101 patients with surgically resected advanced colorectal carcinomas were enrolled. The tumor expressions of Ang-1 and Ang-2 were evaluated immunohistochemically, and their relationships with clinicopathological factors and prognosis were investigated. Tumor microvessel density (MVD) was also calculated and correlated with angiopoietin expression. RESULTS: Ang-1 and Ang-2 were detected in 26 (25.7%) and 45 (44.6%), respectively, of 101 cancerous lesions. Overexpression of Ang-1 was correlated with high MVD. Overexpression of Ang-2 was correlated with lymph node metastasis, venous invasion, preoperative carcinoembryonic antigen levels, and high MVD (P < or = 0.05). MVD was not significantly upregulated by Ang-1 expression, but was significantly upregulated by Ang-2 expression (P < or = 0.01). However, only patients with Ang-2 overexpression showed a significantly worse prognosis than those without Ang-2 overexpression. Multivariate analysis with logistic regression for 5-year survival revealed that cancerous stage and Ang-2 overexpression were independent prognostic indicators. CONCLUSIONS: The Ang-1 expression correlated with MVD. However, Ang-2 expression was a useful prognostic marker in the management of patients with advanced colorectal carcinoma.  相似文献   

4.
目的:采用免疫组化技术,分析DEK基因在结直肠癌患者中的表达情况及其与预后的相关性。方法:运用免疫组化SP法,检测DEK基因在169例结直肠癌患者肿瘤组织及癌旁组织中的表达情况,并运用统计分析软件分析DEK表达水平与结直肠癌患者预后的相关性。结果:DEK的表达率在结直肠癌组织(85/169,50.30%)明显高于癌旁正常组织(28/169,16.57%),差异具有统计学意义(P〈0.01)。DEK在肿瘤组织中的表达情况与病人年龄、性别、肿瘤分化程度、TNM分期及肿瘤大小等因素无相关性,与总生存率(OS)显著相关(P〈0.05)。结论:DEK表达水平与结直肠癌预后密切相关,DEK高表达的结直肠癌患者预后较差。  相似文献   

5.
Rakha EA  Martin S  Lee AH  Morgan D  Pharoah PD  Hodi Z  Macmillan D  Ellis IO 《Cancer》2012,118(15):3670-3680

BACKGROUND:

Although lymphovascular invasion (LVI) has been associated with a poor outcome in patients with breast cancer, it is not included in most internationally recognized staging systems, including the American Joint Committee on Cancer tumor, lymph node, metastasis (TNM) classification. This is mainly because it remains unclear whether the presence of LVI is an independent, high‐risk criterion in clinically relevant staging subgroups.

METHODS:

The current study was based on a large and well characterized consecutive series of patients who had operable (pathologic T1 [pT1]‐pT2, pathologic N0 [pN0]‐pN3, M0) breast cancer (3812 informative cases) who were treated according to standard protocols at a single institution and who had long‐term follow‐up to assess the prognostic value of definite LVI in clinically and molecularly relevant staging subgroups.

RESULTS:

LVI was strongly associated with both breast cancer‐specific survival (BCSS) and distant metastasis‐free survival (DMFS) in the entire series and in different subgroups. Multivariate analyses identified LVI as an independent predictor of both BCSS and DMFS in patients with operable breast cancer overall; in the TNM clinical subgroups pT1a‐pT1c/pN0 and pT2/pN0; and in the molecular classes estrogen receptor (ER)‐positive, ER‐negative, human epidermal growth factor 2 [HER2]‐negative, and triple‐negative. In patients who had lymph node‐negative tumors, LVI could be used as a high‐risk criterion providing survival disadvantage equivalent to that provided by 1 or 2 involved lymph nodes (pN0 to pN1) and to that provided by 1 size category (pT1 to pT2). The use of immunohistochemistry for detecting an endothelial‐specific marker contributed to the prognostic significance of LVI when applied to routine LVI negative/possible cases.

CONCLUSIONS:

LVI provided a strong predictor of outcome in patients with invasive breast cancer and should be incorporated into breast cancer staging systems. Cancer 2012. © 2011 American Cancer Society.  相似文献   

6.
PURPOSE: Metabotropic glutamate receptors (mGluR) play a variety of roles in both neuronal and nonneuronal cells. Recently, we reported that mGluR4 mediates 5-fluorouracil resistance in a human colon cancer cell line. In this study, we evaluated the nonneural expression of mGluR4 and clarified the existence of mGluR4 in normal colon epithelium and colorectal carcinomas. We also investigated the association of mGluR4 expression levels with various clinicopathologic parameters. EXPERIMENTAL DESIGN: mGluR4 expression was investigated in 21 normal and 312 malignant tissues from various organs using immunohistochemistry. In addition, 241 cases of colorectal carcinomas were examined and correlations between mGluR4 expression and various clinicopathologic parameters were then statistically analyzed. RESULTS: Expression of mGluR4 was identified in the normal epithelia of the upper respiratory tract, gastrointestinal tracts, breast, uterine cervix, urinary bladder, and skin, whereas it was not detected in the thyroid, lung alveoli, liver, testis, or prostate. In the corresponding malignant tissues, mGluR4 expression was frequently identified in colorectal carcinoma (68%), followed by malignant melanoma, laryngeal carcinoma, and breast carcinomas. Expression of mGluR4 was detected in 131 (54%) of 241 colorectal carcinomas and 12 (5%) cases among them showed overexpression in their cytoplasms. Loss of mGluR4 expression was negatively associated with tumor differentiation (P = 0.028), whereas overexpression of mGluR4 was positively associated with recurrence (P = 0.034) and poor disease-free survival (P = 0.017) in multivariate analyses. CONCLUSIONS: Our results suggest that mGluR4 signaling may play a role in colorectal carcinomas and that overexpression of mGluR4 is associated with poor prognosis.  相似文献   

7.
OBJECTIVE The present study was designed to evaluate the epidemiological and prognostic significance of proteinuria in patients with gastric cancer (GC).METHODS We retrospectively reviewed the frequency of proteinuria in patients with GC and analyzed its relationship with the GC biological characteristics, treatment and survival.RESULTS Proteinuria incidence in GC patients was 24.06%, which was significantly higher than that found in a control group (P<0.01); the frequency of proteinuria was significantly correlated with an advanced disease stage(P<0.01). We also found that the post-treatment mean value of proteinuria was remarkably lower than the pre-treatment value (P<0.001). KaplanMeier analysis revealed a significant correlation between proteinuria and survival of GC patients (P<0.05). Multivariate analysis demonstrated that the TNM stage, lymph node status and proteinuria may serve as independent prognostic markers in patients with GC (P <0.01).CONCLUSION A high prevalence of increased urinary protein excretion was observed in GC patients complicated with nephritis. Proteinuria may be used as one of the prognostic markers for patients with GC.  相似文献   

8.

BACKGROUND:

Blood vessel invasion has been associated with poor outcome in colorectal cancer (CRC), whereas the prognostic impact of lymphatic invasion is less clear. The authors of this report evaluated venous and lymphatic invasion as potential prognostic indicators in patients with CRC focusing on lymph node‐negative patients and compared routine and review pathology diagnoses.

METHODS:

In total, 381 tumors from randomly selected patients were retrospectively reviewed. The presence of vascular invasion was related to disease‐free and cancer‐specific survival using the Kaplan‐Meier method. For multivariable analysis, Cox proportional hazards regression models were performed.

RESULTS:

Lymphatic invasion and venous invasion were observed in 126 patients (33%) and 87 patients (23%), respectively, and were associated significantly with tumor classification, lymph node status, American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) disease stage, tumor differentiation, pattern of invasion, and extent of tumor budding. The detection of vascular invasion was related to the number of examined tissue blocks. Venous and lymphatic invasion proved to be significant prognostic variables in univariable and multivariable analyses. Extramural vascular involvement was of particular significance. When the analysis was restricted to patients with (AJCC/UICC) stage II disease, venous invasion, but not lymphatic invasion, was identified as an independent prognostic variable. Review pathology diagnoses differed significantly from routine diagnoses with respect to prognostic impact.

CONCLUSIONS:

Venous and lymphatic invasion proved to be significant prognostic variables in patients with CRC. The detection of vascular invasion and, consequently, risk stratification of affected patients were related to the quality of pathology workup, ie, the number of examined tissue blocks. Observed differences between review and routine pathology diagnoses illustrated the need for high‐quality pathology reporting and also for standardized quality control. Cancer 2012;. © 2011 American Cancer Society.  相似文献   

9.
Objective: The membrane-linking protein Ezrin is highly expressed in several types of human cancers. The correlations between its immunoreactivity and histopathological data as well as patient outcome have previously been shown. However, the role played by Ezrin in the carcinogenesis, progression and metastasis of primary sporadic colorectal carcinoma (SCRC) is still under investigation. This study assessed Ezrin protein expression in a series of clinical specimens. Methods: Immunohistochemical analysis was used to characterize patterns of Ezrin expression in 132 cases of SCRC, including 74 metastatic cases and 58 non-metastatic cases and 43 adjacent normal colorectal mucosa. Results: (1) The expression rate of Ezrin in SCRC (79.5%) was significantly higher than in adjacent normal colorectal mucosa (11.6%) (P 〈 0.001); (2) The total expression rate of Ezrin was 86.5% and 70.7% in metastatic group and non-metastatic group, respectively (P = 0.026); the membrane expression rate of Ezrin was 31.1% and 6.9% in the two groups, respectively (P 〈 0.01); (3) There was no relationship between the expression of Ezrin with age, gender, tumor size, location, degree of differentiation and invasive depth; (4) In the cases with followed-up data, univariate analysis demonstrated that Ezrin expression and its membrane translocation was correlated with worse patient's disease-free survival (DFS) (Puni 〈 0.05). Conclusion: Ezrin was expressed in the majority of SCRC and associated with adverse prognostic factors. The increase expression and the switch of Ezrin localization from the cytoplasm to the membrane were closely correlated with metastasis in SCRC. It might be served as an important parameter for determining tumor biological behavior.  相似文献   

10.
The angiogenic factor vascular endothelial growth factor-D (VEGF-D) isa ligand for VEGF receptor-3 (VEGFR-3/Flt-4) and receptor-2 (VEGFR-2/KDR)and is implicated in the development of lymphatic vessels and promotion of lymphatic metastases. We assessed the expression of VEGF-D and VEGFR-3 in relation to microvessel density (MVD) in colorectal carcinomas (CRC), adenomas, and adjacent normal tissue by immunohistochemistry on consecutive archival sections. VEGF-D was detected in malignant and benign epithelium and in some smooth muscle of the colorectum. High-grade VEGF-D expression was observed frequently (74%) in CRC compared with adenomas (0%) and adjacent normal mucosa (22%). High-grade VEGF-D expression was not correlated with MVD, Dukes' stage (A to C), or tumor differentiation, but was associated with lymphatic involvement and patient survival. By multivariate analysis, VEGF-D expression was found to be an independent prognostic factor for both disease-free and overall survival. VEGFR-3 expression was detected in a subset of vessels, typically thin-walled and devoid of RBCs, in 89% of CRC cases examined. VEGFR-3-positive vessel densities increased progressively from normal mucosa to adenomas and carcinomas and were correlated with MVD, but not with Dukes' stage (A to C), tumor differentiation, or VEGF-D expression. VEGFR-3 expression was spatially associated with macrophage-rich inflammatory infiltrates, which were significantly more frequent among VEGFR-3-positive cases. We conclude that VEGF-D expression, but not that of its receptor VEGFR-3, is an independent prognostic indicator in CRC. VEGF-D expression may be associated with disease outcome through the promotion of lymphatic involvement/metastases.  相似文献   

11.
To evaluate the prognostic significance of immunohistochemically detected p53 and Bcl-2 proteins in colorectal cancer, tissue sections from 238 paraffin-embedded colorectal carcinomas were immunostained for p53 (MAb DO-7 and CM-1 antiserum) and Bcl-2 (MAb Bcl-2:124). Staining patterns were assessed semiquantitatively and correlated with each other and with sex, age, tumour site, Dukes'' classification, tumour differentiation, mucinous characteristics, lymphocyte and eosinophilic granulocyte infiltration, and patient survival. In our series, 35% of carcinomas showed no nuclear staining and 34% (DO-7) to 40% (CM-1) showed staining in over 30% of tumour cell nuclei. A majority of carcinomas that had been immunostained with CM-1 showed cytoplasmic staining, but this was not observed with DO-7. With respect to Bcl-2, 51% of tumours were completely negative, 32% displayed weak and 15% moderate staining; only 3% showed strong positive staining. No evidence was found for reciprocity between Bcl-2 expression and nuclear p53 accumulation. From 13 cases containing tumour-associated adenoma, four were Bcl-2 negative in premalignant and malignant cells, in another four cases these cells showed similar staining intensities and in the remaining cases only the malignant colorectal cells were Bcl-2 negative. Therefore, our data indicate that Bcl-2 is dispensable in the progression towards carcinoma. Except for an association between nuclear p53 accumulation and mucinous tumours (P = 0.01), no significant correlation was found between the clinicopathological parameters mentioned above and immunostaining pattern of (nuclear or cytoplasmic) p53 or Bcl-2.  相似文献   

12.
BACKGROUND AND AIM OF THE WORK: Fungal infections are frequent following lung transplantation and are associated with high mortality and morbidity. The study aims at 1) reporting our experience with fungal infections after lung transplantation; 2) identifying statistically significant correlations between the occurrence of fungal infections and bacterial infections, cytomegalovirus disease, rejection and steroid therapy; 3) assessing whether the presence of fungal infection has an impact on long-term survival. METHODS: 60 lung transplant recipients were studied with respect to incidence, pattern of presentation and median time to presentation of fungal infection after the transplant. Correlation analysis of the variables of interest was undertaken in 30 patients who had a minimum follow-up of 1 year following transplant. RESULTS: The prevalence of fungal infection was 44%; severe infections occurred in 5 patients (11%). The presence of Candida preoperatively was not associated with an increased risk of fungal infection. In a logistic regression analysis, a significant correlation was found between the occurrence of fungal infection and the following variables: respiratory bacterial infections (p = 0.0003), cytomegalovirus disease (p = 0.00001) and steroid therapy (p = 0.04). No statistically significant difference was found between patients who experienced a fungal infection and those who did not, either in univariate or multivariate survival analysis (p = 0.08). CONCLUSIONS: 1) fungal infections are frequent in lung transplant recipients and may be severe in more than 10% of the cases; 2) the presence of fungi preoperatively is not a contraindication to transplantation: an antifungal prophylaxis is probably indicated in such cases postoperatively; we recommend the use of the less nephrotoxic liposomal Amphotericin B by aerosol route; 3) a statistically significant association exists between fungal infections and both steroid therapy and CMV disease; this suggests that a similar antifungal prophylaxis is indicated in these clinical circumstances; 4) the presence of fungal infection is not an independent prognostic factor of long-term survival.  相似文献   

13.
The prognosis of colorectal cancer has not significantly changed during the last 30 years. While evaluation of tumour cell proliferation may provide prognostic information, results obtained so far have been contradictory Heterogeneity in tumour cell proliferation may explain these contradictions. With in vivo injection of iododeoxyuridine (IdUrd), estimation of labelling index (LI), S-phase transit time (Ts) and potential doubling time (Tpot) may be performed from a single sample. A total of 109 colorectal cancers were studied after in vivo injection of IdUrd before surgical removal. From each cancer, four to eight samples were processed for both flow cytometrical (FCM) and immunohistochemical (IHC) visualization of IdUrd incorporation. LI/IHC was morphometrically quantified at both the luminal border and the invasive margin of these tumours. LI was significantly higher at the luminal border compared with the invasive margin, although they were correlated with each other. Using combined IHC and FCM methods, rapidly growing colorectal cancers (high LI and/or low Tpot) showed an increased survival (significant for LI at the invasive margin and for Tpot at both the invasive margin and the luminal border) in the entire unselected material and for radically removed Dukes'' B tumours. FCM data alone did not discriminate for survival, with the exception of Ts in diploid and radically removed Dukes'' B tumours.  相似文献   

14.
15.
Lymphovascular and neural invasion in low-lying rectal carcinoma   总被引:1,自引:0,他引:1  
We have previously demonstrated that lymphovascular infiltration was correlated with an increased risk for developing lymph node metastasis in rectal adenocarcinomas confined within the submucosal layer. In another study, lymphovascular infiltration was also correlated with poor prognosis for patients with advanced rectal cancers. Considerations that low rectal tumors have an increased risk to develop recurrence and neural invasion have been recently implicated with a more localized pattern of tumor spread. We therefore assessed the lymphovascular and neural invasion in 65 specimens from patients with low rectal cancers who underwent curative operation to determine its implications in the treatment and prognosis. Lymphovascular invasion was noted in 60%, and neural invasion was found in 27% of the cases. Five-year survival rates (Kaplan-Meier method) were significantly decreased in patients with lymphovascular invasion (31 vs. 67%; p < 0.01) or neural invasion (30 vs. 58%; p < 0.01). Neither lymphovascular nor neural invasion was noted in Dukes' stage A tumors. There was no recurrence or distant metastasis in these patients. However, lymphovascular and neural invasion increased with tumor stage. Local recurrence and distant metastasis occurred respectively in three and four, and five and five patients with Dukes' B and C tumors, respectively. Both Dukes' B and C cases with local recurrence had a higher incidence of neural invasion as compared with the disease-free group. These results suggest that postoperative assessment of venous and neural invasion may provide valuable information to better determine which patients with low rectal cancers would benefit from adjuvant treatment.  相似文献   

16.
The significance of two types of vascular invasion (macroscopic tumor thrombus into the renal vein or vena cava inferior and microvascular invasion) as prognostic factors in renal cell carcinoma is analyzed in 121 patients treated at the Department of Urology, Nara Medical University. The data indicate there to be close correlations between tumor thrombus, microvascular invasion and distant metastasis. In patients with tumor thrombus, however, the prognosis is not as poor when surgical removal of the tumor thrombus is successfully performed as when it is not. In contrast, the prognosis of patients with positive microvascular invasion is significantly worse than that of those with a negative finding. Microvascular invasion appears to be a significant prognostic factor in renal cell carcinoma in addition to well-known factors such as tumor stage, tumor grade, tumor thrombus and distant metastasis. To detect microvascular invasion, the histological examination should be extended to give as much detail as possible.  相似文献   

17.
18.
The molecular biology underlying the metastatic process in ovarian carcinoma remains poorly understood. For other neoplasms, the induction of angiogenesis by malignant cells has been shown to play a pivotal role in the process of tumor proliferation and metastasis. The purpose of this study was to characterize the degree of angiogenesis in epithelial ovarian malignancies and to determine whether the degree of neovascularization has prognostic significance for survival. Tissue sections obtained from 88 ovarian cancer patients were examined immunohistochemically for angiogenesis after staining with anti-human endothelial cell antibodies to von Willebrand factor and CD31. Light microscopy was performed, and individual microvessel counts were quantified at high power (x400). A chart review was completed, collating data regarding age, stage, grade, status of disease, and survival. Statistical exploratory methods were used to find potentially useful prognostic cutpoints for marker values of angiogenesis. Of the total 88 patients, tissue microvessel counts from 85 were evaluated via antibodies to von Willebrand factor and 87 for CD31. Overall, median survival was 2.7 years in women with cancers containing high microvessel counts versus 7.9 years in those with low microvessel counts (P = 0.03). A low microvessel count was associated with better 5-year survival in both early stage (I and II) and advanced stage (III and IV) disease. Our data suggest that the degree of neovascularization may have prognostic significance in epithelial ovarian carcinoma, especially for women with early-stage disease. In this group of women, the degree of angiogenesis may allow the selection of women at high risk for recurrence who may benefit from aggressive adjuvant therapy.  相似文献   

19.
Despite elaborate staging procedures, a substantial number of patients with localized NHL experience dissemination after local therapy, indicating that current routine methods are insufficient to detect tumour spread. We have used flow cytometric clonal excess (CE) analysis of peripheral blood in conjunction with routine staging procedures to study the occurrence of occult leukaemic spread in patients with localized NHL stages I, IE and IIE. CE in peripheral blood was a rare finding, identified in only 11% (14/130), and slightly more frequent in low-grade NHL, 20% compared to high-grade NHL, 7%. There was no correlation to any of the other major prognostic factors studied. Occult tumour spread would suggest an increased risk of relapse and possibly a decreased survival after local therapy. Among 93 patients given only local treatment there was an increased risk of relapse in those with low-grade malignant lymphomas and CE, which was not found in patients with high-grade malignant lymphomas and CE. CE in peripheral blood had no influence on survival in either of the histologic groups. A tentative explanation is that circulating lymphoma cells represent indolent populations irrespective of the histology of the primary tumour. The malignant nature of such a lymphoma spread might not be obvious during this rather limited follow-up of a median 34 months. The clinical interpretation is that the existence of CE in peripheral blood in patients with localized high-grade NHL should have no influence on the choice of therapy. In localized low-grade lymphoma the same therapeutic attitude which applies to widespread disease might be considered.  相似文献   

20.
The Hippo signaling pathway is a critical regulator of organ size control during development, and its deregulation is associated with cancers. Acting downstream of this pathway, Yes-associated protein (YAP) was implicated in tumorigenesis. The present study aimed to explore the expression patterns and clinical significance of YAP in human colorectal cancer (CRC). In addition, we investigated the relationship between YAP expression and Wnt/β-catenin pathway activation in CRC. A total of 139 cases of CRC tissues were investigated by immunohistochemistry for the expression of YAP, cyclin D1, and β-catenin. The association between YAP expression and clinicopathologic features was analyzed. Our results showed that YAP was overexpressed in 52.5 % (73/139) cases of CRC and predominantly presented in the nucleus. There was an excellent correlation between YAP expression and pTNM stage (p?=?0.0024). YAP expression in CRC was significantly correlated with nodal status (p?=?0.0034), tumor status (p?=?0.0382), and cyclin D1 overexpression (p?<?0.0001). Importantly, YAP expression was associated with short overall survival (p?<?0.001). Furthermore, patients with YAP-positive and nuclear β-catenin-positive profiles had worse overall survival. Univariate and multivariate analyses revealed that YAP expression was an independent prognostic indicator of CRC (p?=?0.0207). Our results indicated that YAP overexpression contributed to the tumorigenesis and played a pivotal role in the progression in CRC, and the interaction of YAP and Wnt/β-catenin pathways needs further exploration.  相似文献   

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