The prognostic value of histological grading of posterior fossa ependymomas in children: a Children's Oncology Group study and a review of prognostic factors.

We performed a retrospective analysis of 96 pediatric posterior fossa ependymomas in order to determine the prognostic value of histological grade based on the current WHO grading scheme. The patients were selected among Children's Oncology Group (previously Pediatric Oncology Group-POG) patients enrolled in clinical trials, and on the basis of central pathology review, location, and age. We excluded entities such as sub-ependymoma, myxopapillary, or clear-cell ependymoma, after a consensus diagnosis by three neuropathologists. A total of 66 males and 30 females with a median age of 48 months were identified. The group was analyzed to determine the effects of histological grade, age, gender, and extent of resection on event-free and overall survival. Our results showed that extent of resection, age, and histological grade were independent prognostic variables for event-free survival. The relative risk for extent of resection and histological grade was calculated as 3.59 (P<0.001) and 3.58 (P<0.001), respectively. Overall survival significantly correlated with extent of resection and age, but not with histological grade. We compared our results with peer-reviewed publications on pediatric intracranial ependymomas in the English language between 1990 and 2005. Selection criteria identified 32 manuscripts involving 1444 patients. Extent of resection was a significant factor in 21, age in 12, and histological grading in nine of these studies. Other factors reported to be significant by more than one study included tumor location and radiation treatment. Our findings suggest that histological grade (WHO Grade II vs III) is an independent prognostic indicator for event-free survival, but may not be so for overall survival in pediatric posterior fossa ependymomas. We believe that an accurate assessment of the prognostic value of histological grade depends on the selection of a well-characterized clinical cohort of sufficient size, and the inclusion of relevant histological criteria as outlined in the WHO classification scheme.

P53 gene mutations in surgical margins and primary tumor tissues of patients with squamous cell carcinoma of the head and neck.

AIMS AND BACKGROUND: The frequency of p53 mutations in primary tumors, the effect of the mutations on some clinical and pathological features of head and neck squamous cell carcinoma, and the impact of p53 mutations in the surgical margins on local recurrence were determined, MATERIAL AND METHODS: We investigated the presence of p53 mutations in primary tumor samples and in the surgical margins of 34 patients with head and neck cancer using single strand conformational polymorphism and sequencing analysis. RESULTS: The p53 mutations (codons 175addAT, 175delGC, 206G --> A, and 248delC) were found in the primary tumor samples of 15 of 34 patients (44.12%) and in the surgical margins of 5 of the 15 tumors (33.33%) with p53 mutations. CONCLUSIONS: We found no statistically significant association between the presence of p53 mutations in the primary tumor, the clinical and pathological features, or outcome of head and neck squamous cell carcinoma in this study. Furthermore, the presence of p53 mutations in the surgical margins may not increase the risk of local-regional recurrence, but probably increases the risk of developing distant metastases or second primary tumors.

Expression of cyclin D1 in normal, hyperplastic and neoplastic endometrium and its correlation with Ki-67 and clinicopathological variables.

METHODS: We investigated cyclin D1 expression in proliferative endometrium, endometrial hyperplasia and endometrioid adenocarcinoma, and examined the correlation of cyclin D1 expression with Ki67 as a cell proliferation associated marker. Immunohistochemical expression of cyclin D1 and Ki67 were studied in 30 cases with endometrial carcinoma, 14 cases with atypical hyperplasia, 15 cases with simple hyperplasia and 30 cases with proliferative endometrium. RESULTS: One out of 30 patients (3.3%) with proliferative endometrium, 1 out of 14 patients (7.1%) with atypical hyperplasia, and 8 out of 30 patients (26.6%) with endometrial carcinoma were found to have immunoreactivity to cyclin D1. All cases of simple hyperplasia had negative staining for cyclin D1. A positive immunoreaction for Ki67 was obtained in all cases. Statistically significant difference was found in cyclin D1 immunoreactivity between both proliferative endometrium and adenocarcinoma, and simple hyperplasia and adenocarcinoma (p<0.05). In patients with adenocarcinoma, cyclin D1 immunoreactive cases had higher mean Ki67 values compared with the non-immunoreactive ones (p<0.05). Ki67 and cyclin D1 immunoreactivity had no impact on overall survival. Univariate analysis revealed a significant relationship between survival and grade and stage (p<0.01). Cyclin D1 expression was not correlated with age, depth of myometrial invasion, lymphovascular space involvement, grade, lymph node metastasis and stage. CONCLUSION: Cyclin D1 expression in endometrial carcinoma is higher than proliferative endometrium and simple hyperplasia. These findings support that cyclin D1 may play a role in endometrial carcinogenesis.

A comparison of three histological grading systems in endometrial cancer.

METHODS: To compare the architectural, nuclear and International Federation of Gynecology and Obstetrics (FIGO) grading systems in endometrial cancer 70 consecutive patients with endometrial cancer were retrospectively reevaluated with three grading systems. RESULTS: Twenty-eight (40%), 27 (38.6%) and 14 (20%) cases were reported to have different grades when architectural vs nuclear, architectural vs. FIGO and nuclear vs. FIGO grading systems were compared in evaluation, respectively. Only 3 (42.8%) of the seven died patients had grade 3 in all three grading systems. Five-year survival rates were 95.7, 80, and 78.6% for architectural grade 1, 2 and 3, respectively. Same rates were 96.7, 90.5, and 78.9% for nuclear and 96, 91.7 and 81% for FIGO grading systems, respectively. CONCLUSIONS: Grades of the tumors often change when different grading systems are used. Postoperative treatment should be considered when at least one of the grading systems indicates poor differentiation.

Basaloid squamous cell carcinoma of the larynx: a report of four new cases.

OBJECTIVES: This study is designed to report the clinical and pathologic features and outcome of cases of basaloid squamous cell carcinoma (BSCC) of the larynx treated in our clinic. STUDY DESIGN: A retrospective review of the medical records of these patients. METHODS: Four cases of BSCC of the larynx were treated in our department. Histopathologic slides were reevaluated to confirm the diagnosis. Immunohistochemical studies were performed, and file records were reviewed. Follow-up was available for all patients and ranged between 11 and 72 (mean 37) months. RESULTS: All patients were male (mean 57), with supraglottic or transglottic larynx tumors. Two patients presented with stage-II disease and the other 2 with stage-IV disease. Initial diagnosis was invasive squamous cell carcinoma in 3 patients and BSCC in one patient. Two patients who had stage-II disease underwent partial laryngectomy and bilateral neck dissections; total laryngectomy and bilateral neck dissections were performed in stage-IV patients. Three patients received adjuvant postoperative radiotherapy, and 2 of them also received additional chemotherapy. Patients with stage-IV disease were found to have 4 and 27 metastatic lymph nodes on histopathologic examination and died because of distant metastases at 11 and 14 months, respectively. Patients with stage-II disease did not have cervical metastasis on histopathologic examination and were alive and free of disease at 52 and 72 months respectively. CONCLUSION: In contrast with the literature reporting the tendency of more aggressive clinical behavior of the BSCC, we can say that BSCC has a behavior similar to conventional squamous cell carcinoma based on our 4 cases.

Coexisting endometrial cancer in patients with a preoperative diagnosis of atypical endometrial hyperplasia.

AIM: To investigate the possibility of coexisting endometrial cancer (EC) in patients with atypical endometrial hyperplasia (AEH). METHODS: Forty-six consecutive women who underwent hysterectomy for AEH were analyzed. RESULTS: Final histopathological evaluation of hysterectomy specimens revealed EC in 11 patients (23.9%). Preoperative diagnosis of AEH was established by pipelle biopsy in eight patients and curettage was performed in the remaining patients. Of the patients with pipelle biopsy, two had a diagnosis of EC (25%), whereas nine women who underwent curettage, were further diagnosed as having EC (23.7%) (P > 0.05). Four (13.3%) of 30 women who had frozen sections at hysterectomy, were diagnosed with EC. Diagnosis of EC was missed in two patients (50%) at frozen section. In contrast, seven of 16 women (43.7%) who did not have frozen section, had EC. CONCLUSION: A relatively high incidence of EC is seen in patients with a diagnosis of AEH. Diagnostic results of pipelle biopsy and curettage were comparable. Frozen sections of hysterectomy specimens does not guarantee to exclude the possibility of EC, especially in patients with no myometrial invasion.

Successful salvage therapy of resistant gestational trophoblastic disease with etoposide, methotrexate, actinomycin-D, etoposide, cisplatin (EMA/EP).

A 26-year-old woman who had been treated for nonmetastatic gestational trophoblastic tumor with three courses of methotrexate with folinic acid rescue and had been lost to follow up for 4 years was referred with the fractional curettage diagnosis of choriocarcinoma that had been performed for abnormal vaginal bleeding. Her serum beta human chorionic gonadotropin (betahCG) was 706000 mIU/mL and there were multiple pulmonary metastatic foci. The uterus was 12 weeks pregnant-size and a 6 x 6-cm tumor mass was seen within the anterior uterine wall at ultrasonography. Following total abdominal hysterectomy etoposide, methotrexate, actinomycin-D, vincristine and cyclophosphamide (EMA/CO) regimen was given. Whole brain radiation of 30 Gy in 3 weeks for brain metastasis, discovered in magnetic resonance imaging was given after the first course. Since serum betahCG levels plateaued after three courses of chemotherapy and multiple pulmonary metastases persisted, treatment was shifted to etoposide, methotrexate, actinomycin-D, etoposide, cisplatin (EMA/EP) regimen. She was in remission after three courses of chemotherapy.

Ovarian endodermal sinus tumor in a 76-year-old woman.

A 76-year-old woman underwent surgery for pelvic mass, during which a 13 x 8-cm right ovarian tumor was discovered. On histopathological examination, she was diagnosed with an endodermal sinus tumor with right tubal metastasis. The patient was treated with four cycles of Bleomycin, Etoposide and Cisplatin. She died of disseminated disease four years later.

Angiogenesis in endometrial carcinoma: correlation with survival and clinicopathologic risk factors.

Association among angiogenesis, survival and clinicopathologic parameters in endometrial carcinoma was evaluated. Sixty patients who had been diagnosed as endometrial carcinoma, from 1993 to 1998, were included in the study. All patients had been surgically staged with bilateral pelvic and para-aortic lymph node dissection. All hysterectomy specimens were stained immunohistologically for factor VIII-related antigen. The area with the most intensified microvasculature was determined under low-power (x100) magnification, and the microvessel count of this area under high-power (x200) magnification was determined as the microvessel density (MVD) of the tumor. The mean MVD was 26.2 +/- 13.0 (range 6-68), and it was considered as high (n = 24; 40%), moderate (n = 19; 31.7%) and low (n = 17; 28.3%) when the MVD was >30, between 15-30 and <15, respectively. Statistical analysis included Mann-Whitney, Kruskal-Wallis and Spearman rank correlation tests. The Kaplan-Meier method was used to evaluate the difference between angiogenesis and survival. Multivariate analysis with the Cox regression model was used in MVD values and different clinicopathological parameters. There was positive correlation between MVD increase and surgicopathological stage (p < 0.05). A significant difference was seen between MVD increase and lymph node metastasis (p < 0.05). There were no differences between MVD and age, histological type, grade and lymphovascular invasion. MVD did not change in association with myometrial invasion depth. There was a significant difference in means of survival between the low and high MVD groups (p = 0.01). However, MVD was not an independent prognostic factor in multivariate analysis. Increased angiogenesis was found to be associated with advanced stage and decreased survival in endometrial carcinoma.

Increased risk of chronic hepatitis in children with cancer.

BACKGROUND: There is a risk of viral hepatitis for children with cancer. Both hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in countries with high prevalence cause major problems in the management of cancer patients. In this study, we evaluated the incidence and chronicity of HBV and HCV infections in children with malignant diseases receiving chemotherapy. PROCEDURE: One hundred ninety-eight children with cancer (mean age = 7.5 +/- 2.5 years) and 100 healthy children as a control group were screened for HBV and HCV. Liver function tests, the number of transfusions, HBV and HCV serology were regularly monitored. In seropositive children, HBV-DNA and HCV-RNA were measured. Chronic hepatitis was defined as having an alanine aminotransferase (ALT) level three times of upper normal limit, positive HBV and HCV antigenemia for longer than 6 months. Liver biopsies were performed in all children with chronic hepatitis. The relationship between the chronic hepatitis and study parameters was statistically analyzed. RESULTS: HBsAg positivity, anti-HCV, and mixed (HBV and HCV) infection were found in 11.6, 5.5, 2% of children, respectively. Most HBV infected children developed chronic hepatitis (48%) while 26 and 21.7% became carriers and immune, respectively. One died of acute fulminant HBV hepatitis. Of HCV infected children, 63.6% also had positive HCV-RNA. Four children with mixed infection (100%) all progressed to chronic hepatitis. In this setting, chronic hepatitis was observed in 22 of 38 infected children (57.8%). The majority had leukemia and lymphoma. Children with HBsAg antigenemia developed chronic hepatitis in shorter time than HCV positive children (median 13 months vs. 51 months, P < 0.001). CONCLUSION: We observed an increased incidence of chronic hepatitis and even mortality due to HBV infection. This suggests that HBV and HCV infections are serious causes of morbidity and mortality in children with cancer.

Investigation of genotoxic effect of taxol plus radiation on mice bone marrow cells.

In this study, we investigated the genotoxic effect of taxol, radiation, or taxol plus radiation on highly proliferative normal tissue-bone marrow cells of Swiss albino mice. Swiss-albino mice, 3-4 months old, were used in this study. Taxol was administered bolus intravenously through the tail vein. Radiation was given by using a linear accelerator. There were four treatment categories, which had a total of 34 groups. Each group consisted of five animals. The first was the control category that had one group (n = 5). The second treatment category was taxol alone, which had three groups as per taxol dose alone (n = 15). The third treatment category was radiation alone, which had three groups as per the radiation dose (n = 15). The fourth treatment category was taxol plus radiation, which had 27 groups as per combined radiation dose plus taxol dose concentration and as per pre-treatment timing sequence of taxol before radiation (n = 135). Mice were sacrificed 24 h after taxol or radiation or combined administration using ether anesthesia. The cells were then dropped on two labeled slides, flamed, air dried, and stained in 7% Giemsa; 20-30 well-spread mitotic metaphases were analyzed for each animal; the cells with chromosome breaks, acentric fragments, and rearrangements were evaluated on x1,000 magnification with light microscope (Zeiss axioplan). The mitotic index was determined by counting the number of mitotic cells among 1,000 cells per animal. Differences between groups were evaluated with Student's t-test statistically. Taxol caused a dose-dependent increase in chromosomal aberrations (P = 0.027). Similarly, radiation caused a dose-dependent increase in chromosomal aberrations (P = 0.003) and decreased mitotic index (P = 0.002). In combination, there were a small enhancements at the 40 mg/kg taxol dose level and at 0.25 and 0.5 Gy radiation doses in the 48 h group. However, an increase in chromosomal aberrations was observed after 48 hours of taxol exposure when compared 12 or 24 h of taxol exposure (P = 0.001 and P = 0.019). These findings suggest that taxol at the high doses with low dose radiation caused radiosensitizing effect in bone marrow cells. Forty-eight-hour pretreatment of taxol exposure followed by radiation caused significant induction of chromosomal aberrations and a reduction of mitotic index when compared to other taxol timing sequence.