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Biomedical subjects

D McLemore

Publications and source records attributed to D McLemore.

13 recordsLinked to original sources

DNA ploidy in testicular germ cell neoplasms. Histogenetic and clinical implications.

Flow cytometry was used to determine the DNA ploidy pattern of 148 testicular germ cell neoplasms (seminomas and nonseminomas in pure and mixed histologic phenotypes) and in situ carcinoma (CIS) adjacent to these tumors. The great majority (96.0%) manifested aneuploid DNA contents with minimal intratumoral heterogeneity (2.5%). The mean DNA indices (DI) of CIS (1.7 +/- 0.18), pure seminoma (1.82 +/- 0.55), and the seminoma component of mixed germ cell neoplasms (1.76 +/- 0.13) were statistically similar. The mean DI of nonseminomas pure (1.46 +/- 0.29) or as a component of mixed tumors (1.43 +/- 0.32) was significantly lower (p greater than 0.001) than those of CIS and seminomas. Our data suggest that the similarity between the DNA indices of CIS and seminomas provide evidence that both lesions constitute a temporal evolutionary step in the progression of germ cell tumors and that nonseminomas may subsequently arise from either CIS or seminoma by further loss of chromosomal DNA. These characteristic findings support the nonstochastic theory for germ cell evolution and progression and may be useful in the clinicopathologic evaluation of testicular masses.

Carcinoma in Situ↗

Clear cell sarcomas and metastatic soft tissue melanomas. A flow cytometric comparison and prognostic implications.

Eleven soft tissue clear cell sarcomas (CCS) were examined flow cytometrically for their DNA content with a correlation of the DNA with the patients' survival. Diploidy was expressed in six sarcomas and it conferred a longer survival (mean, 68.6 months) than aneuploid sarcomas (mean, 8.2 months). For comparison, 13 metastases to soft tissues from cutaneous melanomas were assessed by flow cytometric study. The aneuploid neoplasms of both entities were categorized into low and high degree based on extent of the DNA index (DI). Low degree was defined by a DI of less than or equal to 1.5 and high degree by a DI of greater than 1.5. Significant differences in DNA content between CCS and metastatic melanomas were observed. Melanomas were preponderantly aneuploid (11/13) of high degree (mean DI, 1.7) whereas CCS manifested more diploidy (six of 11) and their aneuploidy was of a low degree (mean DI, 1.2; P = 0.001). Clear cell sarcomas and melanomas were also examined for their immunoreactivity to S-100 protein and HMB-45 antigen. All CCS reacted with S-100 protein and HMB-45. In CCS the reactions were diffuse for both in six tumors, diffuse with HMB-45 and moderate to S-100 protein in three tumors and diffuse with S-100 and moderate with HMB-45 in two tumors. All melanomas reacted diffusely to S-100 protein except for one heavily pigmented tumor which reacted only focally. The reaction to HMB-45 was diffuse in nine and focal in three melanomas. These data suggest that measurements of DNA content in CCS may be valuable in predicting clinical outcome and that there are quantitative differences in DNA content between CCS and metastatic melanoma in soft tissues.

Adolescent↗

Uterine stromal neoplasms: a clinicopathologic and DNA flow cytometric correlation.

Twenty-five uterine stromal neoplasms (five stromal nodules and 12 low-grade and eight high-grade stromal sarcomas) were studied to determine the correlation between clinicopathologic features, flow cytometric tumor DNA content and proliferative fraction, and patient outcome. Fifteen of the 20 sarcomas (five of them high grade) were confined to the uterus (stages I and II); the other five (two low grade and three high grade) extended outside the uterus (stages III and IV). Stromal nodules and low-grade sarcomas manifested diploid DNA content and low proliferative index. All stromal nodules and the majority of low-grade sarcomas pursued a benign clinical course. Two cases of low-grade sarcoma ran a malignant course; both patients had high-stage disease. Three of the high-grade sarcomas were diploid and five were aneuploid. All eight neoplasms demonstrated high proliferative index and seven ran a malignant course (four of five were stage I and three of three were stage IV). Three high-grade stage I tumors had a low mitotic rate but a high proliferative index and ran an aggressive course. All high-stage sarcomas were clinically aggressive, irrespective of their histologic classification or DNA characteristics. The proliferative index by flow cytometry may offer an objective adjunct in predicting the aggressive potential of a subset in low-stage neoplasms.

Adult↗

Typical and atypical bronchopulmonary carcinoids. A clinicopathologic and flow cytometric study.

The clinicopathologic and flow cytometric characteristics of 47 bronchopulmonary carcinoids were assessed, relative to patient survival. Aneuploidy was associated more often with tumor size of greater than or equal to 3.0 cm (P less than 0.004) and lymph node (P less than 0.013) or vascular involvement (P less than 0.004). Also, an aneuploid DNA content was seen significantly more often in histologically atypical (79%) than in typical carcinoid neoplasms (18%) (P less than 0.0001). Cox proportional hazard model analysis revealed that the histologic category (typical vs. atypical) and ploidy pattern were important prognostic indicators. Size of the primary tumor and the presence of vascular involvement were also significant predictors of outcome. Histologically atypical carcinoids with diploid DNA content pursued a less aggressive course than did their aneuploid counterparts.

Adolescent↗

Synovial sarcoma. A DNA flow cytometric study.

The relationship between DNA content, clinicopathologic findings, and patient survival in synovial sarcoma was investigated. Patient age at diagnosis (P less than 0.001), tumor size (P less than 0.001), and ploidy status (P less than 0.003) correlated significantly with patient survival. A marginally significant correlation between mitotic count and patient survival was also observed (P = 0.04). Histologic subtypes (monophasic versus biphasic), mitotic count, and S-phase by flow cytometry had no significant influence on the clinical outcome of patients with synovial sarcoma in this study. The authors conclude that DNA ploidy analysis is a significant objective probe in the prognostication of patients with synovial sarcoma.

Adolescent↗

DNA flow cytometry of acinic cell carcinomas of major salivary glands.

Fifteen acinic cell carcinomas from an equal number of patients were analysed for their DNA content and proliferative (S-phase) index by flow cytometry from archival tissues. Seven of the carcinomas manifested a diploid DNA content. None of the patients with diploid acinic cell carcinomas died of their carcinomas and none developed metastases in follow-up periods extending for 10 or more years. Four of eight patients with aneuploid acinic cell carcinomas have died because of their malignancies within a 10 year period after the first surgical removal of the carcinoma. Five of the eight patients exhibited metastases. Although the number of cases does not permit strong correlations between histopathological features, abnormalities in DNA content and outcome of patients, it was noted that carcinomas with prominent necrosis, tubuloductal differentiation and 'dedifferentiated' areas displayed more aggressive biological courses.

Adolescent↗

DNA content and proliferative activity of cystosarcoma phyllodes of the breast. Potential prognostic significance.

Predicting the biologic behavior of cystosarcoma phyllodes of the breast by histopathologic examination has been difficult. Flow cytometric DNA and cell cycle analysis was performed for 30 patients with cystosarcoma phyllodes of the breast to determine its potential prognostic utility. Traditional histopathologic parameters and the patients' clinical outcome with a minimum follow-up period of at least five years were also analyzed. Of all the variables examined, DNA ploidy, proliferative index, number of mitoses, and tumor margin were significantly associated with an adverse clinical course. Multivariate regression analysis of the authors' data showed that DNA content was a significant predictor of the patients' clinical outcome. The authors conclude that the DNA ploidy study is a useful, objective adjunct to the clinicopathologic assessment of cystosarcoma phyllodes of the breast.

Adolescent↗

Clinicopathologic and flow cytometric DNA study of medullary thyroid carcinoma.

Sixty-one patients with medullary thyroid carcinoma were investigated to establish relationships between the neoplasm's DNA content, other clinicopathologic factors, and patient survival (at least 5 years' follow-up). There were 26 (42.6%) familial and 35 (57.4%) sporadic carcinomas. Forty-two neoplasms (68.8%) were diploid and 19 (31.2%) were aneuploid by flow cytometric assessment. In univariate analysis, age, hereditary background, DNA content, calcitonin immunoreactivity, and type of surgery were strong predictors of clinical outcomes. In multivariate regression analysis, none of these factors was an independent prognosticator. Patients' gender, clinical stage, histologic subtype, and amyloid content of the tumor did not influence survival.

Adolescent↗

Renal cell carcinoma. A clinicopathologic and DNA flow cytometric analysis of 103 cases.

Renal cell carcinoma is unpredictable in outcome, although the best predictor is tumor stage, followed by histologic grade. The authors retrospectively assessed the clinicopathologic features and DNA ploidy of 103 cases of renal cell carcinoma, the latter determined by flow cytometry of formalin-fixed, paraffin-embedded tissue. The study group comprised 63 men and 40 women (age, 28-80 years; mean, 57 years). Robson stage at diagnosis was Stage I in 52 patients, Stage II in 21, and Stage III in 30. Statistically significant variables in predicting outcome were Robson stage (P less than 0.0001), DNA ploidy (P = 0.0008), mitotic rate (MR, P less than 0.0001), worst nuclear grade (WNG, P = 0.00009), predominant nuclear grade (P = 0.019), and sex (P = 0.044). Tumor size, cell type, and architectural pattern were also assessed but did not prove to be significant. Statistically significant associations occurred between DNA ploidy and WNG (P less than 0.0001), stage (P = 0.0037), and MR (P = 0.015); between WNG and MR (P less than 0.0001) and stage (P = 0.0007); and between stage and MR (P = 0.002). Cox proportional hazards regression analysis of all significant variables showed Robson stage, tumor ploidy, and MR to be independent, significant predictors of outcome. If ploidy data had not been available, WNG would have been independently significant. The authors conclude that DNA ploidy analysis provides significant predictive information on renal cell carcinoma.

Adult↗

DNA flow cytometry as a predictor of outcome of stage I renal cell carcinoma.

The features most frequently used in predicting the outcome of renal cell carcinoma are stage at presentation and nuclear grade. Recently DNA ploidy pattern, as detected by DNA flow cytometry has also been shown to be predictive. In this study DNA flow cytometry was performed on formalin-fixed paraffin-embedded tissue from 50 patients with Stage I renal cell carcinoma for whom long-term follow-up data were available. Two were eliminated for technical reasons. Of the 48 evaluable tumors, 25 (52%) were diploid, 19 (40%) were nondiploid, and in four, (8%) the ploidy was uncertain. The ploidy pattern was statistically significantly associated with nuclear grade (P less than 0.02), and primary tumor size (P less than 0.05) but did not correlate with cell type, microscopic growth pattern, or the presence or absence of mitotic activity. In the group as a whole, ten patients (21%) died of renal cell carcinoma, seven of 19 (37%) with nondiploid tumor patterns, and two of 25 (8%) with a diploid pattern (P less than 0.03). One of four patients (25%) with tumors of uncertain ploidy also died. However, only two factors, nuclear grade and primary tumor size, were independent predictors of outcome. For Stage I renal cell carcinoma, ploidy can significantly predict patient outcome and correlates with nuclear grade and tumor size, but is not an independent predictive variable.

Carcinoma, Renal Cell↗

Transitional cell carcinoma in high-grade high-stage ovarian carcinoma. An indicator of favorable response to chemotherapy.

We reviewed 53 high-grade carcinomas of the ovary in order to define pathologic features that correlate with prognosis. All tumors were Stage III with comparable amounts of residual tumor left after the primary resection. Similar postoperative chemotherapeutic regimens were given to each patient, and there was a clinical followup of at least four years in each case. The tumors were classified according to their predominant (greater than 50%) histology as transitional cell carcinoma (TCC) (18 tumors), papillary serous (18), undifferentiated (8), or endometrioid (3). There were six mixed carcinomas without predominant histology. In 17 of 18 patients, TCC predominant tumors responded completely to chemotherapy and 15 of 18 patients (83%) are alive without disease 4 to 10 years after presentation (average 6.8 years). In comparison, tumor progression/recurrence developed in 31 of 35 non-TCC tumors (18 serous, eight undifferentiated, one endometrioid predominant, and four mixed carcinomas). Of these 35 patients, 27 (77%) died of disease from 6 months to 7 years after presentation (average 2.5 yrs.). Flow cytometric determination of DNA content and immunoperoxidase studies did not allow discrimination between the histologic types of high-grade ovarian carcinomas. We conclude that TCC should be recognized as a distinct histologic type of ovarian carcinoma because of the favorable response to chemotherapy and improved patient survival.

Carcinoma, Transitional Cell↗

Gastrointestinal stromal tumors: DNA flow-cytometric study of 58 patients with at least five years of follow-up.

Flow-cytometrically measured DNA content of 58 surgically resected gastrointestinal stromal tumors (GIST) was correlated with the lesions' histopathologic features and patients' survival. Aneuploid DNA patterns were found in 43 cases (74%), including 33 (76.7%) histologically malignant and 10 (23.3%) in the indeterminate category. DNA ploidy pattern was significantly correlated with mitotic count (less than 5/10 high power field (HPF) versus greater than or equal to 5/10 HPF, P = 0.04) and histologic grade (malignant versus indeterminate, P = 0.02). DNA content was not related to tumor size, site, or histologic patterns (epitheliod versus spindle). The patients' survival was significantly correlated with DNA content (P less than 0.001), histologic grade (indeterminate versus malignant, P = 0.02), and mitotic rate (less than 5/10 HPF versus greater than or equal to 5/10 HPF, P = 0.01). Multivariate regression analysis showed that DNA ploidy is an independent parameter in predicting the clinical outcome for patients with GIST.

Adult↗