High Histological Grade Tumors Research Articles

Expression of peroxisome proliferator activated receptor-gamma in non-small cell lung carcinoma: correlation with histological type and grade

Peroxisome Proliferator Activated Receptor-gamma (PPAR-γ) is a ligand-activated transcription factor belonging to the steroid receptor superfamily. It is a key regulator of adipogenic differentiation and glucose homeostasis, the ligands of which have also been demonstrated to induce differentiation in human breast, lung and colon cancer cell lines. In the present study, PPAR-γ expression in cases of non-small cell lung carcinoma (NSCLC) was examined immunohistochemically and was correlated with tumor histological type and grade. Primary tumor samples from 147 patients with NSCLC were immunostained using a monoclonal antibody against PPAR-γ. Positive PPAR-γ immunostaining was prominent in 61 out of 147 cases (42%) and negative in the rest. PPAR-γ positivity was prominent in 37 out of 79 cases (47%) of squamous cell lung carcinoma and in 24 out of 68 ones (35%) of lung adenocarcinoma. PPAR-γ positivity was most frequently observed in squamous cell tumors ( P=0.021) and in tumors of high histological grade of both histological types ( P=0.041). Well-differentiated adenocarcinoma cases presented increased frequency for PPAR-γ positivity compared with moderately and poorly differentiated ones ( P=0.001). The intensity and pattern of PPAR-γ staining in tumor cells were not correlated with histopathological parameters in PPAR-γ positive cases of NSCLC examined. Our findings support evidence for participation of this protein in the biological mechanisms underlying the carcinogenic evolution in the lung, suggesting also the importance of specific PPAR-γ ligands as future therapeutic approach in lung cancer.

Quantitative Analysis of BRCA1 and BRCA2 mRNA Expression in Sporadic Breast Carcinomas and Its Relationship with Clinicopathological Characteristics

BRCA1 and BRCA2 mRNA expression in sporadic breast cancers was quantified by a real‐time reverse transcriptase‐polymerase chain reaction (RT‐PCR), and the relationship of their expression with various Clinicopathological factors was studied. BRCA2 mRNA levels (0.993±1.395, mean±SD (BRCA2/β‐glucuronidase mRNA ratios)) were significantly (P<0.01) higher than BRCA1 mRNA levels (0.519±0.570 (BRCAl/p‐glucuronidase mRNA ratios)), and a weak but significant (r=0.390, P<0.01) correlation was observed between BRCA1 and BRCA2 mRNA expression levels. There was no significant association between BRCA1 mRNA expression and Clinicopathological factors such as menstrual status, tumor size, lymph node status, estrogen and progesterone receptor status, and histological grade. On the other hand, there was a significant association between higher BRCA2 mRNA expression and estrogen receptor (ER) negativity (P<0.01) or progesterone receptor (PR) negativity (P<0.01) or high histological grade (P<0.01). These results suggest a differential contribution of BRCA1 and BRCA2 in the pathogenesis of sporadic breast cancers. BRCA2 mRNA is speculated to be up‐regulated in response to proliferation and genomic instability in high histological grade tumors.

Association of Epstein-Barr virus with human mammary carcinoma. Pros and cons.

The Epstein-Barr virus (EBV) is associated with the development of different malignancies. In the last few years, EBV has been detected in a subset of breast tumors. The EBV genome was detected by PCR and Southern-blot analysis and identification of the infected cells was determined using different in situ methods. EBV has detected more frequently in steroid hormone receptors negative tumors, in high histological SBR grade tumors and furthermore, the EBV genome was also observed in metastatic lymph nodes, along with EBV detection in the primary tumor. Opposing results are discussed.

Clinicopathologic study of forty-four histologically pure supratentorial oligodendrogliomas

Few studies in recent years have specifically focused on pure oligodendroglial neoplasms. We retrospectively reviewed the clinicopathologic features of 44 patients with supratentorial oligodendroglioma diagnosed over a 19-year period (1974 to 1993). The study group consisted of 44 patients (age range, 8 to 69 years; median, 42 years), including 31 males. Thirty-one initially resected tumors (70%) were low grade and 13 (30%) were high grade (anaplastic). Using the St Anne-Mayo criteria for astrocytic tumors, 19 tumors (43%) were grade 2, 17 (39%) were grade 3, and 8 were (18%) grade 4. Histologic features of the tumors at initial resection included prominent nucleoli (N = 18, 41%), vascular proliferation (N = 9, 20%), necrosis (N = 6, 14%), and microcystic degeneration (N = 23, 52%). Nuclear atypia was graded as mild in 22 tumors (50%), moderate in 18 (41%), and marked in four (9%). The highest mitosis counts ranged from 0 to 10 mitotic figures (MF)/10 high-power fields (HPF) (mean, 2.4). Twelve patients (27%) had four or more MF/10 HPF. Initial surgery included gross total resection in 10 patients, subtotal resection in 16 patients, and biopsy in 14 patients. Thirty-one patients received adjuvant radiotherapy and 15 received chemotherapy. MIB-1 labeling indices ranged from 0 to 42.3 (median, 1.2 [low grade tumor median, 0.5; anaplastic tumor median, 6.2]). p53 immunostaining was observed in 18 of 43 stained tumors (41%). Overall, 5- and 10-year survival rates were 71% and 63%, respectively. The entire group had a median follow-up of 5.2 years. Age greater than 45 years (P = .02), mitosis counts of > or =4 MF/10 HPF (P = .0004), and MIB-1 labeling indices <2 (P = .03) were independent predictors of survival (Kaplan-Meier analysis). MIB-1 labeling indices <2 (P = .0009) was an independent predictor of disease-free survival. Low cell density (P = .04) and low histologic grade (P = .03) show trends with regard to being associated with longer survival. In conclusion, older patients (>45 years) or patients with tumors with an increased rate of cell proliferation generally have a worse prognosis. Although tumors of high histologic grade generally have a worse survival, the correlation was not statistically significant.

Expression of E-cadherin in 230 infiltrating ductal breast carcinoma

The immunohistochemical expression of E-cadherin (E-CD) was correlated to differentiation grade, tumor size, axillary lymph node metastasis, hormone receptor status and disease outcome in 230 infiltrating ductal breast carcinomas. E-CD expression was reduced in 116 tumors (50.4%). Reduced E-CD expression was more frequently found in high histological grade and progesterone receptor negative tumors. In contrast, preserved E-CD expression was more frequently observed in tumors with axillary lymph node metastasis, particularly in the group of patients with 1 to 3 positive lymph nodes. A weak association between reduced E-CD expression and shortened overall survival was found in univariate survival analysis, that was lost when the patients were adjusted for other pathological factors in multivariate analysis. These data indicate that E-CD may be considered a differentiation marker in ductal carcinomas of non special type. However, the relationship between E-CD expression and lymph node metastasis and disease outcome remains to be established.

A unique pattern of proto-oncogene abnormalities in ovarian adenocarcinomas.

Twelve cases of ovarian adenocarcinoma were studied for alterations in proto-oncogenes, and a unique pattern of altered ras proto-oncogenes was observed. Amplification of ras-Ki was found in three of seven ovarian tumors and amplification of ras-Ha in one of 12. In contrast, ras-Ha amplification was not found in any of the 334 other tumors and ras-Ki amplification was only seen in breast cancer at a frequency of 3%. Other proto-oncogenes altered in ovarian adenocarcinomas included c-myc and c-erbb-2. Proto-oncogene abnormalities were more frequent in aggressive tumors of high histologic grade.

Primary leiomyosarcoma of the vagina: A study of five cases

The clinical and light and electron microscopic features of five cases of primary vaginal leiomyosarcoma, representing 2.9% of all vaginal malignancies registered at the Swedish Cancer Registry, are presented. The ages of the patients ranged from 31 to 69 years. The most common clinical presentation was an increasing mass and/or local tenderness. The tumor was located in the anterior wall in three cases and in the lateral wall in two. The size of the tumors ranged from 2 to over 10 cm. Four patients had tumors of high histologic malignancy grade and were all dead within 36 months. One patient had a tumor of low grade and is still alive 10 years after the initial excision. The ultrastructural observations of abundant myofilaments with focal elongated densities in primary paraffin-embedded material conform with the light microscopic diagnoses in all cases and indicate the usefulness and value of such material for electron microscopy in order to arrive at the diagnosis of leiomyosarcoma. The therapeutic and diagnostic aspects are discussed.

Preoperative whole pelvis versus true pelvis irradiation and/or cystectomy for bladder cancer

Between 1949 and 1974, 449 patients with bladder cancer were treated by radical cystectomy either alone (137 patients or following three preoperative radiation schemes (312 patients). True pelvis irradiation was delivered either 4000 cGy (rad) over 4 weeks in 119 patients, or 2000 cGy over 1 week in 86 patients; radical cystectomy was performed after periods averaging 6 weeks.and 2 days, respectively. Whole pelvic irradiation of 2000 cGy in 5 consecutive days was given to 107 patients who underwent cystectomy within 2 days later. Five-year survival rates for low-stage TIS-T 2 tumors of low histologic grade were 60–66% in the four treatment groups. The 5-year survival for high-stage tumors of high histologic grade, mainly in T 3 patients, was 9% in the cystectomy alone patients versus 24–32% in the preoperatively irradiated patients. The 5-year survival rates for high-stage low-grade and low-stage high-grade tumors, were 30% in the cystectomy alone group and 39–51% in the preoperative irradiation groups; the more favorable survival was noted in the whole pelvic irradiation group, which included 18% 5-year survivals for T 4 patients. Pelvic recurrence was reduced from 28% after cystectomy alone to 14–16% with true pelvis irradiation and 8% with whole pelvic irradiation. The reduced incidence of local recurrence, observed mainly in high stage or high grade tumors, was associated with tumor downstaging after irradiation. Extrapelvic metastases developed in 21–35% of the four treatment groups, underlining the inadequacy of the local radiation and surgical treatment in preventing subsequent distant spread.

Patterns of recurrence in bladder cancer treated by irradiation and/or cystectomy

Between 1949 and 1971, 451 patients with bladder cancer were treated by radiation therapy and/or radical cystectomy at the Memorial Sloan-Kettering Cancer Center. Radical cystectomy alone was the treatment for 137 patients in Group 1. In Group 2, 109 patients received radiation therapy to an average tumor dose of 6000 rad in 6 weeks ± 1 year before radical cystectomy for persistent, recurrent or new lesions. Planned preoperative irradiation consisted of either 4000 rad in 4 weeks for 119 patients in Group 3, or 2000 rad in 1 week for 86 patients in Group 4, ± 6 weeks and 2 days, respectively, before radical cystectomy. The determinate over-all distant and/or local recurrence rate was 49% for Group 1 and 37–45% for Groups 2–4. Local recurrence alone occurred in 28% of Group 1 patients and 14–16% of those in Groups 2–4. Distant metastases developed in 21% of Group 1 patients and 22–28% of Group 2–4 patients. A reduced incidence of pelvic recurrence was associated with radiation-induced stage reduction for Group 2–4 clinically high and low stage tumors, especially when the histologic grade was high. Similar frequencies of extrapelvic metastases in the four groups were maintained in clinically low and high stage tumors of low or high histological grade.