Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The use of non-radioactive in situ hybridization (ISH) with chromosome-specific repetitive DNA probes to study genomic changes, aneuploidy, and heterogeneity during melanocytic tumor progression, relies on its applicability to non-mitotic interphase nuclei, present in cell suspensions and tissue sections. Therefore, we studied the feasibility of detecting numerical aberrations with respect to the (peri-) centromere regions of chromosomes 1 and 7 in intact nuclei of two human melanoma cell lines with different metastatic behavior in nude mice. In addition, we used paraffin sections from xenograft lesions, obtained by inoculation of these cell lines in nude mice (subcutaneous tumors and spontaneous lung metastases). Paraffin sections from the original primary cutaneous melanoma (with a subepidermal and a dermal part) and two loco-regional metastases were also studied, one of which was the source for the cell lines. These cells and tissues represent examples of materials used in different approaches to the study of melanocytic tumor progression. Regarding the targeted sequences, ISH analysis showed that both cell lines were heterogeneous and aneuploid. The results correlated well with those obtained by ISH on metaphase spreads. Differences between the lines, which could not be detected by flow-cytometric or conventional karyotyping analysis, included data suggestive of a polyploid subpopulation and an extra copy of chromosome 7 in the metastasizing cell line. The polyploid population could be detected also in the paraffin sections of the corresponding subcutaneous xenografts and lung metastases in the mice. Both areas in the patients' primary melanoma could be evaluated separately and showed similar supernumerary aberrations of the chromosome-specific targets. These abnormalities matched those found in both metastases. Our results demonstrate that ISH can be used to visualize genomic abnormalities at the single-cell level in melanocytic nuclei in their natural context, which makes it a promising tool in the histopathology of melanocytic lesions and in the study of melanocytic tumor progression.
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PMID:In situ detection of supernumerary aberrations of chromosome-specific repetitive DNA targets in interphase nuclei in human melanoma cell lines and tissue sections. 154 28

Paraffin-embedded tissue sections of primary tumors and lymph node metastases of 80 breast cancer patients were tested for the expression of Thomsen-Friedenreich (TF) antigens with the aid of a monoclonal IgM antibody (49H8) highly specific for phenyl-beta-galactoside. TF antigens were not expressed in 16 different normal tissues with the exception of some structures in the kidney. In tumor cells, two types of antigen expression were found; namely, cryptic and exposed. From stage T1/No to stages T2-4/N1,2 the number of cases expressing high amounts of TF antigens increased from 9% (2/22) to 22% (4/18) while the percentage of patients with low intensity of antibody binding was reduced from 59% (13/22) to 39% (7/18). The total amount of TF-positive primary tumors at stages T2-4/No increased from 42% (8/19) to 69% (18/26) when lymph nodes were infiltrated (T2-4/N1,2). At this stage 80% (21/26) of the patients with lymph node infiltration carried TF antigens in the nodes. The distribution of antigens was heterogeneous among the tumor cells and was expressed mainly in an apical or luminal position. The increased expression of antigens was attributed to exposed TF antigens, while cryptic antigens remained constant. When primary tumors expressed exposed TF antigens, the corresponding lymph nodes also contained exposed antigen. The same was true for the cryptic antigen. The data demonstrate an increase in the intensity of TF antigen expression during tumor progression and a spread of TF-positive tumor cells into the axillary lymph nodes with an increasing number of breast cancer patients being TF-positive at this stage.
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PMID:Increased expression of Thomsen-Friedenreich antigens during tumor progression in breast cancer patients. 342 Mar 74

The purpose of the present study was to investigate the role of p53 in tumor progression of colorectal adenomas and early carcinomas, while especially focusing on flat tumors (depressed adenomas and non-polypoid carcinomas). Paraffin sections of 61 pure adenomas (33 polypoid, 28 depressed), 26 carcinomas in polypoid adenoma (CIA) and 63 pure carcinomas (36 polypoid, 27 non-polypoid) were examined for immunostaining using p53 monoclonal antibody (PAb 1801). All of the carcinomas were restricted to the mucosa. The number and distribution of the p53 positive tumor cells was evaluated, and then compared with tumor growth patterns and histological features. The incidence of p53 expression in carcinomas (58% in CIA and 51% in pure carcinomas) was significantly higher than that in polypoid adenoma (27% in CIA and 21% in pure adenomas). However, the same incidence in depressed adenomas (51%) was significantly higher than in polypoid adenomas. No correlation in carcinomas was observed between p53 expression and clinicopathologic data except for age. The distribution of p53 positive cells was different between adenomas and carcinomas. There tended to be fewer p53 positive cells in adenomas, even in depressed ones, than in carcinomas and they also tended to be confined to the superficial areas in adenomas, while they were diffusely distributed in carcinomas. Interestingly, the p53 positive cells were more frequently present in the deep mucosal areas than in the superficial areas of some non-polypoid carcinomas. In conclusion, the following hypotheses are suggested: (i) the increase of p53 expression from adenoma to carcinoma supports the hypothesis of an adenoma-carcinoma sequence in a polypoid tumor; (ii) the unique p53 expression in non-polypoid carcinoma suggests the existence of another type of carcinogenesis; and (iii) depressed adenomas are thus considered to have a high potential risk of carcinoma.
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PMID:p53 expression patterns in colorectal adenomas and early carcinomas: a special reference to depressed adenoma and non-polypoid carcinoma. 911 Mar 48

Prostate cancer progresses from a localized disease to a widely disseminated malignancy. Each step along this progression pathway involves multiple genetic alterations that impart a survival advantage to the tumor cell over its normal counterparts and may confer resistance to therapy. Because metastatic prostate cancer is one of the most therapy-resistant human neoplasms, we studied the expression of certain molecular determinants of drug resistance in the context of tumor progression. Paraffin-embedded formalin-fixed resected prostates were chosen based on Gleason grade and surgical stage. Immunohistochemistry was used to detect the expression of multidrug resistance protein (MRP), topoisomerase II alpha, p53, glutathione S-transferase pi, Bcl-2, and P-glycoprotein in these specimens. We found that all of the proteins were expressed in resected prostate except for P-glycoprotein. The expression of MRP, topoisomerase II alpha, p53, and Bcl-2 increased with the Gleason grade. In addition, the expression of MRP, topoisomerase II alpha, and p53 increased with the surgical stage. In contrast, the glutathione S-transferase pi and Bcl-2 expression decreased with the increasing surgical stage. Stage was the strongest indicator of protein expression. These results suggest that drug resistance gene products are expressed in prostate cancer at the time of surgical resection. Thus, although the emergence of the "pan-resistance" phenotype in prostate cancer may partly be a function of the selection pressure exerted by therapeutic interventions, certain determinants of chemoresistance may be caused by genetic changes accompanying tumorigenesis.
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PMID:The expression of drug resistance gene products during the progression of human prostate cancer. 962 55

The histological changes of lichen sclerosus (LS) are frequently found in association with vulvar squamous cell carcinoma (SCC). The importance of chronic inflammation and scarring in oncogenesis is well recognized. Thirty-two patients with symptomatic vulvar LS and 60 with vulvar SCC were studied. Paraffin sections of vulvar LS, and three controls groups (acute scars, normal vulva, and vulvar lichen simplex chronicus [LSC]) were investigated with a panel of seven tissue markers and for DNA content in areas without vulvar intraepithelial neoplasia (VIN). All published cases to date of vulvar LS associated with SCC were reviewed. Of the cohort of symptomatic vulvar LS patients (mean/median age, 60 years), 9% developed VIN lesions and 21% invasive SCC; symptomatic LS preceded the carcinoma by a mean of 4 years (range, 1 to 23 years). Second and third primary tumors developed in three of these patients. Of the series of 60 patients presenting with vulvar SCCa, the clinical setting and histological features of SCCs associated with LS were significantly distinctive compared with SCCas without LS: SCCs associated with LS occurred in an older age-group (74 v 65 years; P = .01), were located on the clitoris (41% v 5%; P = .003), were of conventional SCCa type (85% v 57%; P = .02), were associated with a prominent fibromyxoid stromal response (46% v 10%; P = .004), were not associated with VIN 3 (SCC in situ) (5% v 67%; P = .02) and diffusely expressed tumor suppressor gene product p53 (43% v 19%; P = .01) and cytokine TGF-beta (33% v 9%; P = .05). The epidermis of vulvar LS was similar to that of acute scars and differed significantly compared with normal vulva with respect to keratinocytic expression of markers to keratin AE 1, involucrin and filaggrin, epidermal thickness (0.13 mm [LS] v 0.05 mm [normal]; P < .03), and proliferative index by PCNA and Mib-1 labeling (53/60 [LS] v 15/19 [normal] per 200 basal cells [bc]; P < .003). Vulvar LS showed significantly higher expression of p53 than all three control groups (80 [LS] v 3 [normal]/44 [acute scar]/28 [LSC] per 200 bc; P < .008), and aneuploidy (33% v diploid controls) in the absence of VIN. Comparing LS with and without associated SCCa found significant increases in age of patients (74 v 66 years; P = .001), and DNA aneuploidy (52% v 11%; P = .0001) and no differences in epidermal thickness, sclerotic thickness, proliferative index, or p53 expression. However, those cases of LS with an aneuploid DNA content showed significantly elevated p53 expression (88 v 60/200 bc; P = .01) and epidermal thickness (0.16 v 0.11 mm; P = .005) compared with LS with a diploid DNA content. Review of published cases supports an association between LS and vulvar SCC. The phenomenon of chronic inflammation and scarring giving rise to carcinoma has been well documented. Vulvar lichen sclerosus (LS) is an inflammatory dermatosis characterized by clinicopathologic persistence and hypocellular fibrosis (sclerosis). A subset of vulvar SCCs is significantly associated with the presence of LS and diffusely express the p53 gene product. Keratinocytes affected by LS show a proliferative phenotype and can exhibit markers of neoplastic progression such as increased p53 expression and DNA aneuploidy. As a chronic scarring inflammatory dermatosis, vulvar LS could act as both "initiator and promoter" of carcinogenesis, explaining the frequent coexistence of these diseases. Because keratinocytes of LS significantly express tumor suppressor gene p53 protein, the p53 gene may be involved early in this proposed pathway of carcinogenesis.
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PMID:Vulvar lichen sclerosus and squamous cell carcinoma: a cohort, case control, and investigational study with historical perspective; implications for chronic inflammation and sclerosis in the development of neoplasia. 974 9

Tumor progression is associated with the clonal expansion of surviving cell variants. These results in cancer cell heterogeneity and selection of cells with a high malignant potential reflected also by the ability to metastasize. In seeding and implantation of cancer cells at the distant site cell adhesion molecules play a crucial role. Of particular interest is CD44 adhesion molecule, which possibly is involved in tumor metastasis development. Forty cases of an advanced gastric cancer were studied. Paraffin block were collected from the files. In addition to routine tumor typing, grading (Lauren and Goseki classifications) and staging, CD44 (standard, v5 and v6) was studied by immunohistochemistry and RT-PCR. CD44 immunoreactivity was found in 36 of the 40 studied cases. A significant overexpression of CD44v5 was noticed in gastric cancer. This was especially seen in Goseki's grades I and III (72.7% of cases) and was less common in Goseki's grades II and IV (44.4% of cases). CD44v6 was less commonly expressed. In some cases CD44 heterogeneity of neoplastic intravascular emboli was noticed and in some other cases stronger expression of CD44 was present in deeper parts of cancer infiltrate. Immunohistochemical expression was mostly in concert with CD44 gene expression as shown by RT-PCR results. Some discrepancies are discussed. These findings are interesting in view of better prognosis and different route of dissemination of Goseki's grades I + III compared with Goseki's grades II + IV of the gastric cancer. We have shown an overexpression of CD44v5 in an advanced gastric cancer, especially in Goseki's grades I and III. This could reflect a different malignant potential and a different route of dissemination of gastric well differentiated adenocarcinomas.
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PMID:Preferential overexpression of CD44v5 in advanced gastric carcinoma Goseki grades I and III. 1062 17

To analyze relevant factors and their effects on neoplastic progression in cervical carcinoma, a panel of genetic markers was studied. Paraffin-embedded tissue sections were obtained from 37 patients with carcinoma of the uterine cervix, 14 noninvasive squamous cell carcinomas (NISCCs), and 23 invasive squamous cell carcinomas (ISCCs). Immunoreactivity of Msh2, Mlh1, Fhit, p53, Bcl-2, and Bax proteins was examined by immunohistochemical staining with appropriate antibodies. Positive staining of Msh2 was detected in 13 of 14 (92.9%) NISCCs and in 13 of 23 (56.5%) ISCCs (P < 0.02). Mlh1 immunoreactivity was observed in 10 of 14 (71.4%) NISCCs and in 8 of 23 (34.8%) ISCCs (P < 0.04). Overexpression of p53 protein was found in 4 of 14 (28.6%) NISCCs and in 16 of 23 (69.6%) ISCCs (P < 0.02). Bcl-2 overexpression was detected in 2 of 14 (14.3%) NISCCs and in 15 of 23 (65.2%) ISCCs (P < 0.003). No significant difference in the two types of lesion was found for Bax and Fhit expression. The relationship between Mlh1, Msh2, and p53 protein expression was significant (P < 0.001 and P < 0.001, respectively), as was that between Fhit and Bax immunoreactivity (P < 0.02). In conclusion, we consider that altered expression of Msh2, Mlh1, p53, and Bcl-2 may be a critical event during cervical cancer progression, whereas Fhit may be a component of a proapoptotic pathway.
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PMID:Msh2, Mlh1, Fhit, p53, Bcl-2, and Bax expression in invasive and in situ squamous cell carcinoma of the uterine cervix. 1099 51

Lymph node metastasis is a major prognostic factor in human cancer. Vascular endothelial growth factor C (VEGF-C) is a lymphangiogenic polypeptide that has been implicated in several human solid tumors. However, the clinical significance of VEGF-C has remained unknown in gallbladder carcinoma. Paraffin-embedded tumor specimens of 52 surgically resected gallbladder cancers were immunohistochemically stained for VEGF-C, VEGF, and CD34. The correlations among VEGF-C expression, VEGF expression, microvessel density (MVD), clinicopathologic features, and clinical outcomes were statistically analyzed. Thirty-three (63%) of the 52 gallbladder cancers were highly positive for VEGF-C protein by immunohistochemistry. VEGF-C expression was significantly correlated with lymphatic vessel involvement, lymph node metastasis, and worse outcomes after operation (p<0.001, p<0.001, p<0.001, respectively), but not with MVD. By the Cox regression model, lymphatic vessel involvement emerged as an independent prognostic parameter. These results suggest that VEGF-C may play a role in tumor progression via lymphangiogenesis and lymph node metastasis in human gallbladder cancer.
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PMID:Vascular endothelial growth factor-C expression in human gallbladder cancer and its relationship to lymph node metastasis. 1246 14

Cell-cell and cell-extracellular matrix interaction is crucial in tumor progression. Tight junction (TJ) proteins as occludin and claudins (CLDNs) play important role in this process together with several extracellular matrix components, as syndecan. Our previous work suggested significant changes in the expression of claudins even in the early stages of cervical carcinogenesis. The aim of our present work was to study the expression of occludin and syndecan-1, as compared to CLDNs, in early phases of cervical carcinogenesis. Paraffin sections of 50 samples were studied by immunohistochemistry, including cervical intraepithelial neoplasias (CINI-II-III), in situ carcinomas (CIS) and normal cervical samples. Occludin and CLDN-2 were found colocalized in the basal layer, while syndecan-1 and CLDN-1, -4 and -7 were coexpressed in the parabasal and intermedier layers in normal epithelia. Intensity of occludin staining decreased in CIN/CIS lesions, although it was more extended towards the upper epithelial layers with inverse relation with grades, as seen in the case of CLDN-2 expression. CLDN-1, -2, -4 and -7 were detected in the entire epithelium in CIN, showing decrease in CIS. The progression of CIN was associated with reduced syndecan-1 expression, in contrast to CLDN-1, -4 and -7 which increased toward CIS. The obtained data suggest that significant changes occur in the composition of cell adhesion complexes even in early stages of cervical carcinogenesis. The pattern of expression is characteristic for the alteration, the changes in the different components, however, are not parallel with each other.
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PMID:Changes of cell adhesion and extracellular matrix (ECM) components in cervical intraepithelial neoplasia. 1580 Jun 79

Extracellular matrix metalloproteinase inducer (EMMPRIN) is a member of the immunoglobulin superfamily of adhesion molecules and has a role in the activation of several matrix metalloproteinases (MMPs). We evaluated whether EMMPRIN expression is related to tumor progression and patient outcome in human endometrial carcinoma. Paraffin-embedded surgical tissue samples from 112 patients with endometrial carcinoma were stained with anti-EMMPRIN antibody (monoclonal antibody 12C3:MoAb 12C3) for immunohistochemical analysis. EMMPRIN protein was expressed in cancerous lesions with the incidence of 97.3% (109 of 112 cases), but not in normal lesions. The scores determined by the combination of intensity and pattern of EMMPRIN staining in cancer cells correlated significantly with various histopathological risk factors: advanced stage, P=0.001; poorly differentiated carcinoma, P<0.001; lymph node metastasis, P=0.002; and lymphatic vessel infiltration, P=0.027. More importantly, recurrence-free survival was shortened in patients with higher EMMPRIN scores (HR, 3.08; 95% CI, 1.32-7.19; P=0.01). These results suggest that measurement of EMMPRIN expression with simple immunohistochemical staining may enhance the understanding of the pathophysiology of endometrial carcinoma.
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PMID:Association of extracellular matrix metalloproteinase inducer in endometrial carcinoma with patient outcomes and clinicopathogenesis using monoclonal antibody 12C3. 1734 7


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