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Query: UMLS:C0027651 (tumor)
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We investigated the tumor aggressiveness (intratumoral and peritumoral lymphatic and blood vessel invasion by tumor emboli) and proliferative activity (mitotic count) of 45 patients with peripheral, superficially seated, node-negative (T1-2 N0 M0), non-small-cell lung cancer treated with wedge resection alone between January 1982 and June 1988. Most patients were male (n = 39) with T1 (n = 25), small (mean diameter, 2.6 +/- 0.8 cm), squamous (n = 24), right-sided (n = 29) tumors located in either upper lobe (n = 35). The surgical specimens were studied by immunohistochemical staining with a monoclonal antibody targeting the factor VIII-related antigen. None of the tumors had lymphatic peritumoral or intratumoral invasion. Seven neoplasms (15%) harbored blood vessel invasion by tumor cells; all but one of these invasions were within the substance of the tumor. The median mitotic count was 8 mitoses per 10 high-power fields (range, 1 to 42 mitoses), significantly (p = 0.003) higher in patients with blood vessel invasion than in those without. With a 24-month minimum follow-up, projected 3- and 5-year survivals are 79% and 68%, respectively. Eleven patients had relapses and died of their tumors because of either local (n = 5) or extrathoracic (n = 6) recurrence; three patients died without tumors of comorbidity. Among the six tumors recurring in extrathoracic sites, five (83%) harbored intratumoral (n = 4) or peritumoral (n = 1) blood vessel invasion. Both recurrence of disease and death from non-small-cell lung cancer were significantly (p = 0.0009) higher for tumors with blood vessel invasion. By univariate analysis, significant predictors of survival were tumor stage (T1 vs T2, p = 0.008), size (< or = 2.6 cm vs > 2.6 cm, p = 0.039), mitotic count (< or = 8 vs > 8 mitoses, p = 0.0007), and blood vessel invasion (absence vs presence, p = 0.0001). By multivariate analysis, however, only blood vessel invasion retained its level of prognostic significance (p = 0.006). Data demonstrate that peripheral, node-negative non-small-cell lung cancers have a low metastatic potential. Whenever anatomically feasible, wedge resection seems to be an appropriate method of primary treatment.
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PMID:Most peripheral, node-negative, non-small-cell lung cancers have low proliferative rates and no intratumoral and peritumoral blood and lymphatic vessel invasion. Rationale for treatment with wedge resection alone. 145 44

Meningiomas are common tumors of the nervous system. Although usually benign, they may exhibit variable degrees of aggressiveness. Their probability of recurrence after subtotal resection has been correlated with several histological parameters. Independently, a loss of chromosome 22, as evidenced either by cytogenetics or by somatic loss of alleles, has been observed in about half of the cases studied. In 34 meningiomas we have examined the relationship between loss of chromosome 22 alleles and 6 histological predictors of recurrence. Significant correlations were found for 3 of these, i.e. prominent nucleoli (p less than 0.002), microscope count of mitoses (p less than 0.05) and nuclear pleomorphism (p less than 0.02). Correlation with the other 3, i.e. sheeting of cells, vascularity and micronecrosis, did not reach significance. Total tumor score, defined by the sum of the individual scores for these 6 parameters, was strongly correlated to allelic loss (p less than 0.0001). Thus, the loss of chromosome 22 alleles, which possibly contribute to the inactivation of tumor-suppressor gene(s), might be a potent genetic marker of the aggressiveness of meningiomas.
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PMID:Allelic loss on chromosome 22 correlates with histopathological predictors of recurrence of meningiomas. 134 29

The expression of the protooncogene encoded proteins (c-erbB1, c-erb B2, c-myc, c-fos) and the suppressor gene product p53 was analyzed in 81 human squamous cell carcinomas of the lung and correlated with clinical parameters of the patients (patient survival, presence of metastases and tumor stage) and with biological characteristics of the tumors (tumor growth in nude mice, DNA-ploidy, proliferative activity, drug-resistance and P-glycoprotein or gluathione S-transferase expression). By means of immunohistochemistry, expression of c-erbB1 oncoprotein (EGF-receptor) was detected in 79% of the tumors, c-erbB2 (c-neu) proteins in 35%, c-myc proteins in 48%, c-fos proteins in 41%, and p53 in 43% of the tumors. Patients with c-erbB1 positive tumors had a poor prognosis (p = 0.021). In addition, these tumors were more frequently drug resistant (p = 0.0067). A significant correlation between the growth of the squamous lung carcinomas in nude mice and c-fos oncoprotein expression was demonstrated (p = 0.017). Therefore, EGF-receptor and c-fos products may serve as prognostic factors for the aggressiveness of squamous cell carcinomas of the lung and for the response of these tumors to chemotherapy. No significant correlation was found between the expression of the c-erbB1 or c-fos gene products and stage, metastasis and DNA-ploidy. In contrast to these results, no relationship was found between c-neu or c-myc gene products expression and any of the clinical or biological parameters examined. Aneuploid squamous cell carcinomas of the lung expressed p53 more frequently than diploid tumors (p = 0.027). However, there was no significant difference between p53 expression and stage, survival of patients, metastasis, growth of the tumors in nude mice, proliferative activity and drug-resistance of the tumors.
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PMID:Oncoprotein (c-myc, c-erbB1, c-erbB2, c-fos) and suppressor gene product (p53) expression in squamous cell carcinomas of the lung. Clinical and biological correlations. 134 20

To search for differentially expressed gene products in selected cancers of endodermal origin, cDNA libraries derived from mRNA in human hepatocellular carcinoma and adjacent grossly normal tissue were generated. From these parent libraries, subtracted cDNA libraries of tumor minus normal and normal minus tumor tissues were constructed. After screening these subtracted libraries by +/- hybridization, a cDNA clone that is overexpressed in hepatocellular carcinoma and encodes the human acidic ribosomal phosphoprotein P0 (P0) was identified. We then evaluated the expression of this phosphoprotein P0 in human colon carcinoma samples. Surgical specimens of primary tumors and liver metastases were examined by Northern hybridization of total RNA with one of 2 32P-labeled P0 probes. The mRNA level of the P0 was greater in primary colon carcinoma than in paired adjacent normal colonic epithelium in 36 of 38 cases; the mean tumor/normal ratio was 2.7 (range, up to 13). The tumor/normal ratio, when plotted against the Dukes' stage of disease, gave evidence for increasing P0 expression with increasing stage of colon carcinoma (P = 0.02). In all 8 cases of paired colon carcinoma metastatic to liver and 2 cases of paired primary hepatocellular carcinoma, the P0 mRNA level was greater in tumor than in adjacent normal liver tissue. The mean tumor/normal ratio was 4.0 (range, up to 11) for the colon cancers metastatic to liver and 4.2 for the primary hepatocellular carcinoma samples. These findings support a common increased expression of selected gene products in different tumors of endodermal origin and suggest that increased P0 expression, in line with certain other ribosomal proteins, may be associated with human colorectal cancer progression and biological aggressiveness.
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PMID:Increased expression of human ribosomal phosphoprotein P0 messenger RNA in hepatocellular carcinoma and colon carcinoma. 135 May 8

The extent and the variation of losses of genetic material were examined in a series of 191 human breast cancers by means of a set of 18 polymorphic DNA probes, specific of 7 chromosomal arms (1p, 1q, 3p, 11p, 13q, 17p and 18q) known to be frequently affected by allele losses. Frequencies of losses of heterozygosity ranged from a low of 3.5% (chromosome 13q) to a high of 27% (chromosome 3p). The number of sites involved in breast cancer added to the frequent occurrence of concomitant losses at several chromosomal arms within the same tumor suggest cooperative effects of these LOHs. We were therefore interested in assessing the existence of preferential associations between sets of LOHs in our panel of tumors. Statistically significant associations were found between LOHs at chromosomes 1p and 17p, and between LOHs at chromosomes 11p and 17p. Furthermore, since all the tumors presently studied had previously been analyzed for proto-oncogene amplification at 5 distinct chromosomal sites, we tested for associations between LOH and DNA amplification. Such associations were indeed observed as exemplified by the correlations observed between the LOH at 11p and amplification of the erbB2 gene and LOH at 17p and the amplification of the flg gene. The only correlation with clinico-pathological parameters that could be observed linked the occurrence of LOHs on 11p with recurrent breast cancer (p = 0.015). Sets of several LOHs or LOHs and gene amplifications could not be significantly related to any marker of tumor aggressiveness.
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PMID:An attempt to define sets of cooperating genetic alterations in human breast cancer. 135 Oct 44

In order to analyze the correlation between immunohistochemical positivity for c-erbB-2 oncoprotein and prognosis in patients with malignant salivary gland tumors, 59 cases of malignant tumors of the major salivary glands, including 35 parotid gland, 20 submaxillary gland and 4 sublingual gland tumors, were studied immunohistochemically using a polyclonal antibody against c-erbB-2 oncoprotein. Positive staining was observed in 13 (22%) of the 59 cases. Interestingly, positive results were obtained only in adenocarcinoma (6/20) and carcinoma in pleomorphic adenoma (7/15), and not in any other histological types such as adenoid cystic carcinoma, mucoepidermoid tumor, and squamous cell carcinoma. There was no correlation between the degree of differentiation of adenocarcinoma and c-erbB-2 positivity. Since the carcinoma in pleomorphic adenoma positive for c-erbB-2 oncoprotein was adenocarcinoma, adenocarcinoma and adenocarcinoma in pleomorphic adenoma were placed together (n = 33), and the presence or absence of c-erbB-2 oncoprotein in this group was examined for correlation with patients' survival and other clinicopathological features, including clinical stage, tumor size, surgical margins, and lymph node status. The c-erbB-2-positive tumors tended to be more advanced and larger than negative tumors. Similarly, c-erbB-2-positive tumors were difficult to resect completely, were associated with lymph node metastasis more frequently, and showed lower disease-free survival than negative cases (P less than .05). We conclude that immunohistochemical positivity for c-erbB-2 is an indicator of aggressiveness in both adenocarcinoma and adenocarcinoma in pleomorphic adenoma of the major salivary glands.
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PMID:Immunohistochemical study of c-erbB-2 oncoprotein overexpression in human major salivary gland carcinoma: an indicator of aggressiveness. 135 53

Squamous cell carcinoma of the upper aerodigestive tract presents significant problems in determining appropriate treatment regimens. Staging aided by sophisticated investigations allows for planning of treatment, but there is a definite need for a specific and reproducible marker to quantify biological aggressiveness. For some classes of tumors the DNA ploidy of cells, as determined by flow cytometry, has shown good correlation to pathologic grading and prognosis. Using a mathematical model, it is possible to calculate the S-phase fraction, which is indicative of proliferative activity and may reflect tumor aggressiveness. However, this parameter is often difficult to determine reliably in squamous cell carcinoma. An optimal marker would be a measureable protein related to proliferation. An attempt was made to use flow cytometry to measure the nuclear enzyme topoisomerase II to assess proliferation in cultured cell lines. Although the antibody was specific to the extracted protein, constituents of the rabbit serum bound non-specifically throughout fixed cells. Further purification of this antibody preparation could realize its diagnostic potential. Antibody against proliferating cell nuclear antigen was more specific, resulting in good correlation flow cytometrically with the S-phase fraction of the cultured cell lines. The results obtained with these protein markers deems further investigation into their use as prognostic indicators. The protocol has been established to apply this technology to tumor samples and establish a meaningful parameter of biological behavior of tumors, upon which treatment regimens can be confidently based.
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PMID:Measurement of proliferative index in squamous cell carcinoma by flow cytometry. 136 86

Current opinions differ as to the biological significance and treatment of pure seminoma associated with the serological establishment of beta-human chorionic gonadotropin. Between December 1987 and April 1990, 147 patients with malignant testicular tumors were treated. Of these patients 47 (32%) had a pure seminoma. In 35 of the 47 patients we measured the tumor markers beta-human chorionic gonadotropins and alpha-fetoprotein in the cubital vein blood and testicular vein blood. There were elevated beta-human chorionic gonadotropin levels in the cubital veins of 26% of the patients, in agreement with the literature. However, elevated levels were found in the testicular veins of 80% of the patients, which reflects the high sensitivity of marker identification in testicular vein blood. Apparently, most seminomas produce beta-human chorionic gonadotropin even if it is not detectable in the cubital vein. We believe that the presence of this marker in patients with pure seminoma is not an indication of greater tumor aggressiveness but of tumor mass.
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PMID:Spermatic cord beta-human chorionic gonadotropin levels in seminoma and their clinical implications. 137 58

Carcinoma of the prostate is the most commonly diagnosed cancer in men. The natural history and the biological aggressiveness are primarily determined by tumor volume. At the time of diagnosis, only one third of all tumors are pathologically confined to the prostate and eligible for curative therapy. Early detection by the general practitioner with prostate-specific antigen and digital rectal examination should be the primary goal. Currently, diagnosis is best established by transrectal ultrasound-guided biopsies. For the treatment of localized prostate cancer, men who undergo radical retropubic prostatectomy have been shown to have superior long-term results when compared to those who have received radiation therapy. With an improved understanding of the prostatic anatomy and nerve-sparing surgical techniques, morbidity from impotence and incontinence are minimal. In advanced carcinoma, 70 to 80% of men initially respond well to androgen withdrawal. Unfortunately, androgen-independent cells will continue to multiply, leading to tumor progression and death. Until effective chemotherapeutic agents are developed, we can only achieve palliation in advanced disease.
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PMID:[Prostate carcinoma--a current review]. 137 72

The prognostic significance of microvessel quantitation in invasive breast carcinoma was analyzed in a study group that comprised 88 patients with axillary node-negative carcinoma and 32 patients with axillary node-positive carcinoma who had a minimum follow-up period of 9 years. Microvessels were identified by immunohistochemistry using antibodies to endothelial markers, including factor VIII-related antigen and blood group isoantigens (ABH). Factor VIII-related antigen staining provided more consistent results for microvessel quantitation than did staining for ABH isoantigens. The three most vascular areas within a tumor were selected, and the microvessels within a x200 microscopic field of each area were counted by two investigators simultaneously. Node-positive carcinomas demonstrated significantly higher microvessel counts than did node-negative carcinomas (mean +/- SD, 99 +/- 42 and 73 +/- 22, respectively; P less than .001). In node-negative carcinomas, tumors from patients who experienced distant recurrence had higher microvessel counts than did tumors from patients who were disease-free (84 +/- 19 and 70 +/- 22; P = .01). Similarly, in patients with node-positive carcinoma, microvessel counts were considerably higher in tumors from patients who experienced distant recurrence than in patients who did not, although the difference did not reach statistical significance (113 +/- 44 and 93 +/- 34, respectively). Among patients with node-negative carcinoma, those with a microvessel count of less than 84 had a recurrence rate of 20% compared with 57% in patients with counts greater than 84 (P = .003). Microvessel counts were independent of histologic parameters, ploidy status, and S-phase fraction but correlated with peritumoral vascular invasion. Both microvessel counts and vascular invasion were independent prognostic parameters by multivariate analysis. High vessel counts may represent increased tumor angiogenesis and are correlated with tumor aggressiveness. Microvessel quantitation may be an additional prognostic factor that, when used in conjunction with more established parameters, can help in appropriate patient management.
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PMID:Microvessel quantitation and prognosis in invasive breast carcinoma. 137 62


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