Intact PTEN Expression by Immunohistochemistry is Associated With Decreased Survival in Advanced Stage Ovarian/Primary Peritoneal High-grade Serous Carcinoma.

Ovarian high-grade serous carcinoma is an aggressive malignancy with poor prognosis. Optimal surgical debulking and tumor sensitivity to platinum-based chemotherapy are 2 well-established prognostics for this tumor type. Molecular markers that identify more clinically aggressive tumors would potentially allow for the development of individualized treatment options. PTEN is a key negative regulator of the PI3K signaling pathway. Loss of PTEN expression in endometrial carcinoma is associated with endometrioid histology; women with endometrioid tumors have a better prognosis than those with nonendometrioid tumors. The prognostic and predictive value for PTEN has not been effectively explored in ovarian/peritoneal high-grade serous carcinoma. PTEN immunohistochemistry was assessed in 126 women with Stage III, high-grade serous carcinoma of the ovary/peritoneum treated with surgery and then a platinum-based regimen. Compared with PTEN-negative or PTEN-reduced tumors, positive PTEN immunohistochemistry, detected in 58% of tumors, was associated with decreased pS6 and increased PTEN mRNA levels. Positive PTEN expression was independent of surgical debulking status or platinum sensitivity. PTEN-positive tumors were associated with significantly decreased recurrence-free survival. Importantly, the devised PTEN immunohistochemistry scoring system was reproducible among pathologists.

Image quality and dose performance of 80 kV low dose scan protocol in high-pitch spiral coronary CT angiography: feasibility study.

To investigate the image quality and dose performance of 80 kV high-pitch spiral (HPS) coronary CT angiography (CCTA). 106 patients consecutively enrolled into prospectively ECG-triggering HPS CCTA (pitch = 3.4) exam using kV/ref. mAs = 80/400, 100/370, and 120/370 when patient BMI was ≤22.5 (n = 40), between 22.5 and 27.5 (n = 53) and >27.5 kg/m² (n = 13). Image quality was assessed per-segment by two observers independently using a 4-point scale (1-excellent, 4-non-diagnosable). Image noise and signal-to-noise ratio (SNR), contrast-to-noise ratio were measured. Diagnostic image quality was obtained in 503 of 507, 687 of 693, 164 of 167 coronary segments in 80, 100, 120 kV groups without significant difference (P = 0.482). The proportions of segments with score 1-4 were not significantly different among three kV groups (all P > 0.05). Image noise were significantly higher in 80 kV group than 100 and 120 groups (P < 0.001), while SNR was not (P = 0.097). The effective dose of 80 kV group (0.36 ± 0.03 mSv) was significantly lower than that of 100 kV group (0.86 ± 0.08 mSv) and 120 kV group (1.77 ± 0.18 mSv). The mean ± SD of HR in all patients was 54.8 ± 5.1 bpm. 80 kV HPS CCTA is feasible for patient with BMI ≤ 22.5 kg/m² which can save 58% dose than 100 kV group, while maintain diagnosable image quality.

Molecular clustering based on ERα and EIG121 predicts survival in high-grade serous carcinoma of the ovary/peritoneum.

Assessment of estrogen receptor (ER) expression by immunohistochemistry has yielded inconsistent results as a prognostic indicator in ovarian carcinoma. In breast and endometrial carcinomas, panels of estrogen-induced genes have shown improved prognostic capability over the use of ER immunohistochemistry alone. For both breast and endometrial cancers, overexpression of estrogen-induced genes is associated with better prognosis. We hypothesized that analysis of a panel of estrogen-induced genes can predict the outcome in ovarian carcinoma and potentially differentiate between tumors of varying hormonal responsiveness. From a cohort of 219 women undergoing ovarian cancer surgery from 2004 to 2007, 83 patients were selected for inclusion. All patients had advanced stage ovarian/primary peritoneal high-grade serous carcinoma and underwent primary surgical debulking, followed by adjuvant treatment with platinum and taxane agents. The expression of ERα and six genes known to be induced by estrogen in the female reproductive tract (namely EIG121, sFRP1, sFRP4, RALDH2, PR, and IGF-1) was measured using quantitative RT-PCR. Unsupervised cluster analyses were used to categorize patients as high or low gene expressors. Gene expression results were then compared with those for ER immunohistochemistry. Clusters were compared using χ(2) analyses, and Cox proportional hazards models were used to evaluate survival outcomes. The median follow-up time was 38.7 months (range: 1-68). A cluster defined by EIG121 and ERα segregated tumors into distinct groups of high and low gene expressors. Shorter overall survival (OS) was associated with high gene expression (HR 2.84 (1.11-7.30), P=0.03), even after adjustment for other covariates. No difference in ER immunohistochemistry expression was noted between gene clusters. In contrast to other hormonally driven cancers, high expression of ERα and the estrogen-induced gene EIG121 predicts shorter OS in patients with high-grade serous ovarian carcinoma. Such a biomarker panel may potentially be used to guide management with estrogen antagonists in this patient population.

Clinicopathological features in endometrial carcinoma associated with Lynch syndrome in China.

OBJECTIVE: To study the clinicopathological characteristics of Lynch syndrome-associated endometrial carcinoma in China. METHODS: Twenty-seven patients who fulfilled Amsterdam criteria II were classified as having Lynch syndrome-associated endometrial carcinoma (group A), and 331 patients without a family history of cancer were classified as having sporadic endometrial carcinoma (group B). RESULTS: There were 81 malignancies in 27 families with Lynch syndrome-associated endometrial carcinoma, including colorectal cancer (24.7%), endometrial carcinoma (21.0%), and liver (12.3%), stomach (9.9%), lung (6.2%), and breast (6.2%) cancers. Mean age at the time of diagnosis was 49.7 years in group A and 56.3 years in group B (P = 0.004). Second primary cancers occurred in 33.3% of patients in group A and 5.1% in group B (P = 0.000). The most common second primary cancers were colorectal cancer (44%) and ovarian cancer (22%). The percentage of obese patients was higher in group A (P= 0.013). There was no difference between the 2 groups in incidence of diabetes mellitus or hypertension or in histological type and International Federation of Gynecology and Obstetrics stage. The 5-year survival rates for groups A and B were 96.2% and 79.6%, respectively. Prognosis for group A was better than for group B (P = 0.045). CONCLUSIONS: Some clinicopathological features of Lynch syndrome-associated endometrial carcinoma, such as early onset and multiple primary carcinomas are similar in the Chinese and American/European populations. However, the Chinese population had a unique family cancer distribution that included lung and breast cancers. Well-differentiated grade and good prognosis imply better biobehavior of Lynch syndrome-associated endometrial carcinoma in the Chinese population.

[The value of spiral computed tomography in diagnosis of adult intussusception].

OBJECTIVE: To evaluate the value of spiral computed tomography (CT) in diagnosis of adult intussusception. METHODS: Sixty-eight patients with adult intussusception, 42 males and 28 females, aged 52.5 (30-82), with the course of 3 days-13 months, underwent plain CT scanning and biphase CT enhanced scanning of the abdomen. Operation was performed later. RESULTS: Sixty-six of the 68 patients (97.1%) were diagnosed as with intussusception by spiral CT. Direct signs of intussusception were shown in 66 patients: concentric circle sign in 66 cases, vessel involvement in 61 cases, and fat sign in 58 cases. And main indirect signs were shown in 19 cases: ring sign in 19 cases, ileus sign in 24 cases, and ascitic fluid sign in 4 cases. Other signs included mesenteric infiltration in 4 cases and retroperitoneal lymphadenectasis in 8 cases. Operation performed later showed an accurate rate of etiological diagnosis of intussusception by CT of 72.1%. CONCLUSION: Spiral CT has important value in diagnosis of adult intussusception and its etiology. The specific signs to diagnose adult intussusception are concentric circle sign, vessel involvement and fat sign.

Rapid detection of IgH/BCL2 rearrangement in follicular lymphoma by interphase fluorescence in situ hybridization with bacterial artificial chromosome probes.

Follicular lymphomas (FLs) can be difficult to diagnose on aspirated specimens since the architectural pattern is not present. FLs characteristically have rearrangements in the IgH and BCL2 genes resulting from the reciprocal t(14;18) (q32; q21) translocation. Because of the dispersed distribution of breakpoints, fluorescence in situ hybridization (FISH) using genomic probes that span or flank the breakpoints is ideal for detecting this rearrangement in fine-needle aspiration (FNA) biopsies. To develop a set of probes, a bacterial artificial chromosome library was screened and the clones were mapped by fiber FISH. The probes were produced by the direct incorporation of fluorochrome-labeled nucleotides. The colocalization base FISH assay was applied to Cytospin preparations from FNA biopsies of lymph nodes from 26 patients with FL and 10 patients without FL. In those with FL, the percentage of cells with at least one IgH/BCL2 fusion signal ranged from 22% to 100% (mean, 63%), which was statistically significantly higher than that in FL-negative samples (mean, 2.7%). The probes demonstrated a significantly lower cutoff value (7%) in normal controls and effectively reduced the false-positive rate in FL-negative cases. These results were confirmed with fiber FISH assays on the same specimens. This interphase FISH assay is rapid and reliable for detecting rearrangements in the IGH/BCL2 gene, thereby aiding in the diagnosis of FL on FNA biopsy specimens.