Invasive Front (invasive + front)

Distribution by Scientific Domains
Distribution within Medical Sciences


Selected Abstracts


Prognostic Significance of Matrix Metalloproteinase-7 (MMP-7) Expression at the Invasive Front in Gastric Carcinoma

CANCER SCIENCE, Issue 3 2002
Xiu Ping Liu
To evaluate the clinicopathological significance of matrix metalloproteinase-7 (MMP-7) expression in gastric carcinoma, we investigated immunohistochemically MMP-7 expression in 214 gastric carcinomas, and examined its relations with the clinicopathologic parameters including patient prognosis. MMP-7 expressed predominantly in cancer cells, and MMP-7-positive tumor cells were preferentially found in deeply invading nests, especially at the invasive front. The mean MMP-7 labeling index (LI) at the invasive front was significantly higher in tumors invading or penetrating the muscularis propria and in stages II-IV than within the submucosal layer and in stage I, respectively (P<0.001). Statistical analysis revealed that MMP-7 LI at the invasive front was related to lymph node metastasis, vascular invasion, and lymphatic permeation, when all 214 cases were examined as one group (P<0.05 for all), and the cases with high MMP-7 expression at the invasive front showed significantly more unfavorable prognosis as compared with that of low MMP-7 expression tumors (P<0.01). Multivariate analysis revealed that TNM stage and MMP-7 expression status at the invasive front were independent prognostic factors (P=0.0017, relative risk (RR)=3.12; P=0.0019, RR=2.67, respectively). Our findings indicated that expression of MMP-7 at the invasive front is closely associated with local invasiveness, and might be a reliable prognostic marker for patients with gastric carcinoma. [source]


Prognostic factors of clinically stage I and II oral tongue carcinoma,A comparative study of stage, thickness, shape, growth pattern, invasive front malignancy grading, martinez-gimeno score, and pathologic features

HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 6 2002
Anthony Po Wing Yuen FHKAM(ORL)
Abstract Purpose This study aims at evaluation of the different prognostic models, including stage, tumor thickness, shape, malignancy grading of tumor invasive front, Martinez-Gimeno score, and pathologic features in the prediction of subclinical nodal metastasis, local recurrence, and survival of early T1 and T2 oral tongue squamous cell carcinoma. The results will have important implication for the management of patients. Patients and Methods Seventy-two clinically T1 and T2 glossectomy specimens of oral tongue carcinoma were serially sectioned in 3-mm thickness for the evaluation of various pathologic features. The prognostic value in the prediction of subclinical nodal metastasis, local recurrence, and survival of different models were compared. Results Among all the tumor parameters and predictive models being evaluated, tumor thickness was the only significant factor that had significant predictive value for subclinical nodal metastasis, local recurrence, and survival. With the use of 3-mm and 9-mm division, tumor of up to 3-mm thickness has 8% subclinical nodal metastasis, 0% local recurrence, and 100% 5-year actuarial disease-free survival; tumor thickness of more than 3 mm and up to 9 mm had 44% subclinical nodal metastasis, 7% local recurrence, and 76% 5-year actuarial disease-free survival; tumor of more than 9 mm had 53% subclinical nodal metastasis, 24% local recurrence, and 66% 5-year actuarial disease-free survival. Conclusions Tumor thickness should be considered in the management planning of patients with early oral tongue carcinoma. © 2002 Wiley Periodicals, Inc. Head Neck 24: 513,520, 2002 [source]


Heterogeneous expression of Wnt/,-catenin target genes within colorectal cancer

INTERNATIONAL JOURNAL OF CANCER, Issue 9 2007
Falk Hlubek
Abstract Invasion of common colorectal adenocarcinomas is coupled with a transient loss of epithelial differentiation of tumor cells. Previously, we have shown that dedifferentiated tumor cells at the invasive front (IF) accumulate the transcriptional activator ,-catenin in the nucleus, in contrast to cells of the tumor center. To characterize the cells of these two morphogenic tumor areas, gene expression profiling was performed. Our study demonstrates that intratumorous heterogeneity in colorectal cancer correlates with differential expression of 510 genes between the central tumor region (TC) and the IF. Many genes differentially expressed at the IF are involved in cellular invasion processes like cell motility, cell adhesion and extracellular matrix interaction. This in vivo analysis shows overexpression of known Wnt/,-catenin target genes either in the entire tumor tissue (compared to normal mucosa) or specifically at the IF. Thus, even though all tumor cells overexpress ,-catenin, the existence of at least 2 groups of Wnt/,-catenin target genes selectively activated in different tumor regions is suggested. The concomitant high expression of inflammation- and tissue repair-related genes at the IF supports the hypothesis that an inflammation-activated microenvironment may trigger selective Wnt/,-catenin target gene expression and contribute to the malignant progression of colorectal cancer. © 2007 Wiley-Liss, Inc. [source]


Expression of plasminogen activator inhibitor-1, urokinase receptor and laminin ,-2 chain is an early coordinated event in incipient oral squamous cell carcinoma

INTERNATIONAL JOURNAL OF CANCER, Issue 12 2006
Pia Lindberg
Abstract Cancer cell invasion is facilitated by extracellular matrix degrading proteases such as plasmin. We have studied the expression of plasminogen activator inhibitor-1 (PAI-1) and urokinase receptor (uPAR) together with the ,2-chain of laminin-5 (lam-,2) by immunohistochemistry in 20 cases with incipient oral squamous cell carcinoma (SCC). PAI-1-positive neoplastic cells located at the tip of the putative invasive front of grade 1 (incipient) carcinoma were seen in 16 of the 20 cases (75%), whereas adjacent normal and dysplastic epithelium was PAI-1-negative. Clusters of putative invasive neoplastic cells located in the lamina propria were PAI-1-positive in areas with grade 2 incipient carcinoma as were invasive cancer cells in areas of grade 3,4 invasive carcinoma. uPAR immunoreactivity was strongly expressed in numerous stromal cells in the carcinoma area in all 20 lesions, while a few uPAR-positive stromal cells were found in areas with normal and dysplastic epithelium. uPAR-positive neoplastic cell islands located at the front of the lesions were seen in 15 of the 20 cases. The expression pattern of lam-,2 was very similar to that of PAI-1; however, lam-,2-positive neoplastic cells were only detected in 11 of the 20 cases (55%) in areas of grade 1 incipient carcinoma. Direct comparison of the 3 components revealed colocalization in neoplastic cell islands in both incipient and invasive SCC. Our results suggest that PAI-1 is a novel potential marker of initial invasion in oral SCC, and that the coordinated expression of PAI-1 with uPAR and lam-,2 sustain the features of the early invasive cancer cells. © 2006 Wiley-Liss, Inc. [source]


Low-grade dysplasia component in early invasive squamous cell carcinoma of the esophagus

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 2 2010
Yuichi Shimizu
Abstract Background and Aims:, It has not been determined whether low-grade squamous dysplasia (LGD) of the esophagus is a precancerous lesion or not. If LGD progresses to squamous cell carcinoma, early carcinoma lesions that have such a natural history might contain a remaining LGD component. Methods:, The lesions in the 68 patients with early invasive squamous cell carcinoma who underwent endoscopic mucosal resection were examined for the presence of an LGD component. If LGD components were observed, the degrees of architectural and cytological abnormalities of LGD components and those of tumor invasive fronts in the same lesions were studied. The degrees of abnormalities of 28 small LGD lesions were also studied. Results:, Histological examination of resected specimens confirmed LGD components in 43% of the squamous cell carcinoma lesions. The lesions of lamina propria mucosae (m2) cancer contained a significantly broader area of LGD component than did the lesions of muscularis mucosae (m3) and submucosal layer (sm) cancer (P = 0.037). Mean score for the degrees of cytological abnormalities of LGD component was similar to that of tumor invasive front (P = 0.457) and significantly higher than that of small LGD lesions (P < 0.001). Conclusion:, Our results indicate the possibility that the lesion was formed by a combination of small lesions that arose as a multicentric occurrence of squamous cell carcinoma and dysplasia. Our results also suggest that an LGD component would transform to carcinoma along with tumor progression. However, the concept of ,basal cell layer type carcinoma in situ' may be suitable for squamous cell lesions with a high degree of cytological abnormalities confined to the lower half of the epithelium. [source]


Correlation of basic fibroblast growth factor expression with the invasion and the prognosis of oral squamous cell carcinoma

JOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 3 2006
Takashi Hase
Background:, The aim of this study was to evaluate the relationship between the expression of basic fibroblast growth factor (bFGF) and fibroblast growth factor receptor-1 (FGFR-1) in cancer cells and fibroblasts at the invasive front of oral squamous cell carcinoma (OSCC), and the pathologic and clinical characteristics. Methods:, Sections of 61 biopsy specimens of primary OSCC were immunostained to assess the expression of bFGF and FGFR-1 in cancer cells and fibroblasts at the invasive front. Results:, The bFGF and FGFR-1 expressions in the cancer cells were evident in all specimens, whilst, in fibroblasts, they were detected in 41 (67%) of 61 specimens. These expressions in the fibroblasts occurred notably more often in high-invasive OSCC specimens than low-invasive OSCC specimens. The prevalence of bFGF and FGFR-1 expressions in cases with lymph node metastasis was significantly higher (P < 0.05) than in cases without metastasis. Moreover, these expressions were well correlated with patient prognosis. Conclusion:, This study concludes that bFGF and FGFR-1 expressions in fibroblasts at the invasive front are linked to the mode of invasion and the prognosis in OSCC. [source]


Cdx2 transcription factor regulates claudin-3 and claudin-4 expression during intestinal differentiation of gastric carcinoma

PATHOLOGY INTERNATIONAL, Issue 3 2008
Shinya Satake
According to the expression of gastric (claudin-18) and intestinal claudins (claudin-3 and claudin-4), the authors have previously proposed a new phenotypic classification of gastric carcinoma (GC): the gastric (G-CLDN), intestinal (I-CLDN) and unclassified claudin (U-CLDN) phenotypes. The aim of the present study was to examine the role of Cdx2, the caudal -related transcription factor, on the regulation of intestinal claudins expression in vitro and in vivo. It was confirmed on immunohistochemistry that non-neoplastic gastric mucosa with intestinal metaplasia (IM) expressed Cdx2 with increased levels of intestinal claudin expression. In addition, Cdx2 expression was detected in 28 (30%) of 94 GC at the invasive front. Interestingly, Cdx2 expression had a significant association with the I-CLDN phenotype (P < 0.001), which was almost identical to the established gastric and intestinal mucin-based GC classification. Furthermore, the transfection of a recombinant human CDX2 -expressing vector into TMK-1 (Cdx2-negative) GC cells specifically elevated the expression of claudin-3 and claudin-4 at the mRNA (CLDN3, 3.9-fold; CLDN4, 2.8-fold) and protein levels (claudin-3, 8.6-fold; claudin-4, 9.8-fold), whereas no induction of the other claudins was detected. These findings suggest that Cdx2 plays an important role in the regulation of intestinal claudin expression not only in gastric mucosa with IM but also GC. [source]


Transcriptional upregulation and unmethylation of the promoter region of p16 in invasive basal cell carcinoma cells and partial co-localization with the ,2 chain of laminin-332,

THE JOURNAL OF PATHOLOGY, Issue 1 2007
S Svensson Månsson
Abstract Basal cell carcinoma cells show low proliferation rates at the invasive front and a concordant upregulation of the cdk-inhibitor p16, limiting proliferative capacity. Little is known about the mechanisms of p16 regulation in normal and malignant cells apart from that many transcription factors such as Ets1, Ets2, SP1, SP3, JunB and the polycomb protein Bmi1 have the potential to induce or repress p16 expression. Therefore, the aim of this study was to determine how p16 is regulated in basal cell carcinoma with special focus on its upregulation in invasive cells. By analysing various microdissected areas of basal cell carcinoma using real-time quantitative PCR we observed upregulation of p16 mRNA in invasive tumour cells compared to centrally localized tumour cells. The methylation status of the p16 promoter, analysed by methylation-specific PCR, also showed diminished methylation in tumour cells at the invasive front, supporting the hypothesis that promoter methylation can affect the transcriptional activation of p16 in vivo. There was only sporadic co-localization of Ets, or ERK1/2 phosphorylation with p16 upregulation at the invasive front, suggesting that these factors were not directly involved in the regulation of p16. Furthermore, the ,2 chain of laminin-332 has been reported to be increased at the invasive front compared to the central areas of many tumours. Interestingly, in basal cell carcinoma we observed partial co-localization between p16 and the ,2 chain of laminin-332 in tumour cells towards areas of ulceration and in the majority of clearly infiltrative tumour cells but not in p16 positive tumour cells with a more pushing invasive growth pattern. These data suggest that concurrent p16 upregulation and decreased proliferation are more general phenomena in different types of invasive growth patterns in basal cell carcinomas and that these only partially overlap with the ,2 chain of laminin-332 associated invasion patterns. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source]


Increased Expression of Laminin-5 and Its Prognostic Significance in Hypopharyngeal Cancer,

THE LARYNGOSCOPE, Issue 7 2004
Meijin Nakayama MD
Objectives: We investigated the clinicopathologic significance of laminin-5 ,2 chain (LN,2) expression in 26 surgically removed hypopharyngeal cancers and compared the results with conventional prognostic factors elicited from hematoxylin-eosin (H&E) stained whole-mount laryngeal sections. Study Design: Stainability of LN,2 was mainly evaluated at the invasive front of the cancer nests. Scoring was performed on the basis of a semiquantitative scale defined according to the number of immunopositive cancer cells (score 3, 2, 1, and 0). Stainability of LN,2 was also evaluated macroscopically at different tumor locations such as surface center, interstitial space, and invasive front. Status of cartilage and vascular invasion and patterns of tumor extension were evaluated from H&E stained sections. The results of LN,2 expression correlated with the tumor stages, neck node status, pathologic differentiation, and prognoses. Results: Among the 26 cases, 24 demonstrated positive LN,2 expression. Of these cases, 1, 14, 9, and 0 showed scores of 3, 2, 1, and 0, respectively. Positive expression of LN,2 at the invasive front was more prominent in the high-expression group, and surface center was often positive in the cases of low-expression group. Among the H&E stained prognostic factors, vascular invasion and infiltrative pattern demonstrated significant correlations with clinical outcome. Vascular invasion and infiltrative pattern were also closely related to positive LN,2 expression. Five-year survival rates of patients who showed high LN,2 expression were significantly poorer than in patients with low expression. Conclusion: Hypopharyngeal cancers positive for LN,2 indicate a considerable risk for cancer progression and are closely related to prognosis. Increased LN,2 expression might be a prognostic indicator for squamous cell carcinomas of the hypopharynx. [source]


Differential expression of hMLH1 in sporadic human colorectal cancer tumors and distant metastases

APMIS, Issue 11 2009
NICOLAI BALLE LARSEN
Somatic defects in the mismatch repair system constitute an important pathway in colorectal carcinogenesis. We have examined the expression of mismatch repair proteins in sporadic stage IV colorectal tumors and their derived metastases. Sporadic tumors were further examined for differences in expression between the tumor transition zone and the invasive front. Expression of hMSH2, hMLH1, and hPMS2 was screened immunohistochemically in 92 stage IV tumors and derived liver metastases. In cases with loss of mismatch repair protein expression, lymph node metastases were also examined. Clinicopathological parameters and Ki-67 staining indexes were evaluated and compared. Four tumors displayed a complete loss of hMLH1/hPMS2 expression at the transition zone; however, three of these expressed both proteins at the invasive front and in liver and lymph node metastases. A further four were predominantly hMLH1/hPMS2 negative at the transition zone, but with distinct subclones of hMLH1/hPMS2-expressing cells at the transition zone. All of these tumors expressed hMLH1/hPMS2 at the invasive front and in liver metastases, with three also expressing hMLH/hPMS2 in lymph node metastases. No significant difference in the proliferative index was observed for the hMLH1/hPMS2-compromised group. In stage IV tumors re-expression of hMLH1/hPMS2 occurred, leading to different patterns of expression within the primary tumor and between tumor and metastases. This may have functional importance for the chemosensitivity of metastases compared to the primary tumor. [source]


Tumor volume of colon carcinoma is related to the invasive pattern but not to the expression of cell adhesion proteins

APMIS, Issue 3 2009
VICTORIA HAHN-STRÖMBERG
Tumor volume increases during growth and due to tumor progression various mutations appear that may cause phenotypic changes. The invasive pattern may thus be affected resulting in a more disorganized growth. This phenomenon might be due to mutations in the genome of the adhesion proteins, which are responsible for the structural integrity of epithelial tissue. Tumor volume was assessed in whole mount sections of 33 colon carcinomas using Cavalieri's principle. Images from the entire invasive border were captured and used for calculating the irregularity of the border (Complexity Index). The expression of the adhesion proteins E-cadherin, ,-catenin, Claudin 2 and Occludin was assessed after immunohistochemical staining of two randomly selected areas of the invasive front of the tumor. Statistical significance for differences in volume was obtained for tumor Complexity Index, tumor stage (pT) and lymph node status (pN). Expression of adhesion proteins was significantly perturbed in the tumors compared with normal mucosa but only infrequently correlated to tumor differentiation or invasive pattern. The results show that when tumor volume increases the invasive pattern becomes more irregular which is compatible with tumor progression. A direct contribution of adhesion protein derangement to this process appears to be insignificant. [source]


Expression of C4.4A at the invasive front is a novel prognostic marker for disease recurrence of colorectal cancer

CANCER SCIENCE, Issue 10 2010
Ken Konishi
Metastasis-associated gene C4.4A is a glycolipid-anchored membrane protein expressed in several human malignancies. The aim of this study was to explore the expression and clinical relevance of C4.4A in colorectal cancer. By quantitative RT-PCR, 154 colorectal cancer tissues were examined for C4.4A mRNA. We examined 132 colorectal cancer tissues by immunohistochemistry using a new polyclonal antibody that recognizes the C4.4A protein C-terminus containing the glycosylphosphatidyl-inositol anchor signaling sequence. A significant difference in 5-year overall survival was found between samples with high and low expression of C4.4A mRNA (P = 0.0005). Immunohistochemistry showed strong membranous staining of C4.4A at the invasive front of colorectal cancer tumors and at the frontier of metastatic lesions to lymph node and lung. The membranous staining with enhanced intensity at the invasive front of the primary colorectal cancer (Type A: 34/132, 25.6%) was associated with depth of invasion (P = 0.033) and venous invasion (P = 0.003), and was a significant independent prognostic factor (5-year overall survival in the entire series [n = 132; P = 0.004] and disease-free survival in stage II and III colorectal cancers [n = 82; P = 0.003]). Moreover, Type A C4.4A expression was linked to shorter liver metastasis-free survival rate, lung metastasis-free survival rate, or hematogenous metastasis-free survival (P = 0.0279, P = 0.0061, and P = 0.0006, respectively). Our data indicate that expression of the C4.4A protein at the invasive front acts as a novel prognostic marker in colorectal cancer, possibly through invasion-related mechanisms. (Cancer Sci 2010) [source]


Comparison of cell proliferation in the centre and advancing fronts of oral squamous cell carcinomas using Ki-67 index

CELL PROLIFERATION, Issue 5 2003
U. Dissanayake
A comparison was made between the indices derived from the centre of the tumours and those derived from the invasive fronts of the same tumours. There was a positive correlation between the two indices suggesting a clonal expansion of malignant cells, but the mean index derived for the invasive fronts (29.75 11.64) was significantly higher than the mean index for the body of these tumours (25.65 11.64). Thus, at a given time, more peripheral cells at the invasive front are proliferating and this compartment is likely to be more informative in prognostic and other behavioural studies involving the cell cycle. In squamous carcinomas, increased and uncontrolled cell proliferation at the invasive front may be one feature contributory to the invasion. [source]


Low-grade dysplasia component in early invasive squamous cell carcinoma of the esophagus

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 2 2010
Yuichi Shimizu
Abstract Background and Aims:, It has not been determined whether low-grade squamous dysplasia (LGD) of the esophagus is a precancerous lesion or not. If LGD progresses to squamous cell carcinoma, early carcinoma lesions that have such a natural history might contain a remaining LGD component. Methods:, The lesions in the 68 patients with early invasive squamous cell carcinoma who underwent endoscopic mucosal resection were examined for the presence of an LGD component. If LGD components were observed, the degrees of architectural and cytological abnormalities of LGD components and those of tumor invasive fronts in the same lesions were studied. The degrees of abnormalities of 28 small LGD lesions were also studied. Results:, Histological examination of resected specimens confirmed LGD components in 43% of the squamous cell carcinoma lesions. The lesions of lamina propria mucosae (m2) cancer contained a significantly broader area of LGD component than did the lesions of muscularis mucosae (m3) and submucosal layer (sm) cancer (P = 0.037). Mean score for the degrees of cytological abnormalities of LGD component was similar to that of tumor invasive front (P = 0.457) and significantly higher than that of small LGD lesions (P < 0.001). Conclusion:, Our results indicate the possibility that the lesion was formed by a combination of small lesions that arose as a multicentric occurrence of squamous cell carcinoma and dysplasia. Our results also suggest that an LGD component would transform to carcinoma along with tumor progression. However, the concept of ,basal cell layer type carcinoma in situ' may be suitable for squamous cell lesions with a high degree of cytological abnormalities confined to the lower half of the epithelium. [source]


Comparison of cell proliferation in the centre and advancing fronts of oral squamous cell carcinomas using Ki-67 index

CELL PROLIFERATION, Issue 5 2003
U. Dissanayake
A comparison was made between the indices derived from the centre of the tumours and those derived from the invasive fronts of the same tumours. There was a positive correlation between the two indices suggesting a clonal expansion of malignant cells, but the mean index derived for the invasive fronts (29.75 11.64) was significantly higher than the mean index for the body of these tumours (25.65 11.64). Thus, at a given time, more peripheral cells at the invasive front are proliferating and this compartment is likely to be more informative in prognostic and other behavioural studies involving the cell cycle. In squamous carcinomas, increased and uncontrolled cell proliferation at the invasive front may be one feature contributory to the invasion. [source]