BIRC2 amplification in squamous cell carcinomas of the uterine cervix.

Oncogene amplification is a key step in cell transformation towards malignancy. Chromosomal aberrations involving the long arm of chromosome 11, including amplifications at 11q13 and 11q22, have been previously reported in cervical cancer. While the role of the CCND1 gene as the driver gene for 11q13 amplification is well established in different tumor types, the significance of the 11q22 amplicon is less clear. The 11q22 amplicon corresponds to several putative target genes including the apoptose inhibitor BIRC2, recently detected as amplified in cervical cancer cell lines. To better understand the distribution and frequency of 11q amplification sites in uterine cervical carcinomas, we analyzed BIRC2 and CCND1 copy number changes using fluorescence in situ hybridization in a tissue microarray containing 238 cervical cancers. High-level amplification of BIRC2 was found in 12.9 % of tumors. Amplification of BIRC2 in cervical carcinomas was homogeneous as shown in corresponding whole tissue sections of amplified tumors at the tissue microarray. BIRC2 amplification was significantly more frequent than CCND1 amplification (2.1 %) in our cohort (p < 0.01), and amplification of both genes were independent from each other. BIRC2 amplification was associated with younger-patient age (p < 0.05) and squamous cell differentiation (p = 0.025) of cervix carcinomas. However, BIRC2 copy number changes were not related to tumor stage, grading and nodal status of cervical cancers. In conclusion, BIRC2 is amplified in a subset of squamous cell carcinoma of the uterine cervix. Further studies are necessary to evaluate possible prognostic effects of BIRC2 copy number gains in cervical carcinomas.

EGFR gene copy number increase in vulvar carcinomas is linked with poor clinical outcome.

EGFR copy number increases have been frequently reported in cancer including vulvar carcinomas. Co-amplification of cancer genes plays an important role in the development of many tumour types. To better understand the effect of EGFR aberrations on vulvar cancer phenotype and patient prognosis, the authors analysed EGFR copy number changes using fluorescence in situ hybridisation and EGFR expression by immunohistochemistry in a tissue microarray containing 183 squamous cell carcinomas of vulva. Furthermore, the authors analysed the co-amplification frequency of EGFR with HER2, CCND1, MYC and PIK3CA, respectively. EGFR copy number increase was found in 39.3% of the tumours. Seventeen per cent of vulvar carcinomas showed EGFR high polysomy including 9% with amplification of the EGFR gene. Copy number gain of the EGFR locus was associated with non-basaloid phenotype (p=0.03), high-tumour stage (p<0.001), human papillomaviruse negativity of tumours (p=0.04) and the number of lymph node metastases (p=0.02). EGFR protein expression was statistically correlated to EGFR copy number increase (p<0.05). The observed co-amplification rate of EGFR with all four additionally examined oncogenes was much higher than statistically expected. There was a highly significant association between EGFR copy number increase and CCND1 amplifications (p<0.001) as well as the total number of gene amplifications (p=0.04). EGFR copy number gains were significantly related to unfavourable patient outcome in univariate analysis and multivariate Cox regression analysis. In conclusion, EGFR copy number increases are detectable in a substantial proportion of vulvar carcinomas with relationships to advanced tumour stages and the development of lymph node metastases. EGFR copy number aberrations are connected to other gene amplifications and probably define an human papillomaviruses-independent pathway in the development of vulvar carcinomas. These data support the potential utility of EGFR inhibitors as a therapeutic alternative in a subset of vulvar carcinomas.

Health-related quality of life and patient-defined benefit of clobetasol 0.05% in women with chronic lichen sclerosus of the vulva.

BACKGROUND: This study investigates the health-related quality of life in patients with vulvar lichen sclerosus (LS) and the patient-defined therapeutic benefit of clobetasol. METHODS: A survey analysis of 96 women with LS after treatment with clobetasol was performed. Quality of life was assessed with the Skindex-29. The Patient Benefit Index (PBI) was used to determine the therapeutic benefit. RESULTS: The overall response rate was 59.2%. Quality of life was most impaired by somatic symptoms (scale 'Symptoms' score 3.2) and emotional stress (scale 'Emotions' score 3.1), while social interactions (scale 'Functioning' score 1.9) played an inferior role (p < 0.001). Primary therapeutic goals 'to have confidence in the therapy' and 'to be free of itching' were achieved in 73.2 and 69.0% of patients who indicated the goal applied to them. The global PBI score was 3.06. In 93.2% of patients it was >1, indicating a potential benefit from clobetasol. CONCLUSION: Topical clobetasol is of potential therapeutic benefit for patients with vulvar LS and might therefore improve quality of life.

Clinical management of borderline ovarian tumors.

Borderline ovarian tumors (BOTs) are epithelial tumors of the ovaries characterized by cellular proliferation and nuclear atypia but without an infiltrative growth pattern. As they frequently affect younger patients the clinical management is complicated by considerations such as preserving fertility and reducing postoperative morbidity. Over the past several decades surgical therapy has shifted from a radical approach to more conservative treatment. There are various modes of surgery applied to the patients. All these developments have to be considered from an oncologic standpoint as BOTs represent a potentially malignant disease. Oncologic safety, as well as patients' desires and expectations, have to be balanced to reach the most appropriate treatment for BOTs. For this reason current literature will be discussed in this review to give a thorough overview of this topic and to develop recommendations for the surgical management of these patients. Open questions will be identified to elaborate the need for future surveys and research.

Perioperative morbidity and outcome of secondary cytoreduction for recurrent epithelial ovarian cancer.

BACKGROUND: Despite radical surgical and chemotherapeutic treatment of ovarian cancer, the majority of patients develop recurrent disease. Secondary cytoreductive surgery can result in favourable outcome in selected patients, but information regarding feasibility, safety and perioperative outcome of these often complex procedures is limited. METHODS: Surgical parameters in patients with recurrent epithelial ovarian cancer selected for secondary cytoreduction were analysed and compared to patients undergoing primary cytoreduction. RESULTS: In total, 222 patients undergoing radical cytoreduction were analysed (48 patients for relapsed disease and 174 patients at primary diagnosis of advanced ovarian cancer). The range of surgical procedures was similar in both groups. In 48% of secondary cytoreductions 'optimal surgical results' (residual tumour <1 cm) were obtained and 33% of the patients had no residual disease compared to 82% and 58% at primary cytoreduction. There was no significant difference in perioperative complication rates. The duration of surgery was shorter and the number of transfused blood products was smaller at secondary cytoreduction (p < 0.001 and p = 0.001). CONCLUSION: Secondary cytoreduction in relapsed ovarian cancer is safe and feasible and perioperative outcome is not inferior compared to primary cytoreduction. Surgery-associated morbidity should represent a minor aspect in the selection and counselling of patients regarding treatment options for recurrent ovarian cancer.

HER-2/neu analysis in breast cancer bone metastases.

BACKGROUND: HER-2 is the target for antibody-based treatment of breast cancer (trastuzumab), which is highly successful in both advanced disease and the adjuvant setting. HER-2 can be analysed by fluorescence in situ hybridisation (FISH) for gene amplification or immunohistochemistry (IHC) for protein overexpression. AIM: As both methods are known to be influenced by previous tissue processing, to analyse the applicability of both FISH and IHC to decalcified bone metastases of breast cancer. METHODS: A tissue microarray (TMA) was constructed from 149 breast cancer bone metastases. Consecutive TMA sections were analysed by FISH (PathVysion) and IHC (HercepTest). RESULTS: FISH analysis was interpretable in 113 (85.0%) cases. Amplification was seen in 14 (12.4%) interpretable metastases. HER-2 positivity on IHC analysis was 3+ in 9.8% of cases and 2+ in 11.3%. A comparison of the two techniques revealed high concordance. Of the 14 cases of amplification, 10 (71%) showed 3+ IHC staining, two (14%) showed 2+, one (7%) showed 1+, and one (7%) showed 0+. Three of the four amplified cases that did not show 3+ IHC staining had an equivocal FISH result, with a HER-2/centromere 17 ratio of 1.8-2.2. Of the 13 cases that showed IHC 3+ staining, amplification was present in 10 (77%). CONCLUSIONS: HER-2 FISH analysis has an excellent success rate in highly standardised EDTA-decalcified bone metastases, suggesting that this method is easily applicable to decalcified tissues. The high concordance between IHC and FISH suggests that HER-2 IHC may be equally applicable to EDTA-treated tissues as to the usual formalin-fixed tissues.

Quality of life among breast cancer patients undergoing autologous breast reconstruction versus breast conserving therapy.

PURPOSE: Besides the quality of the aesthetic results, the quality of life after surgery is one of the most important criteria when reviewing different operation methods, especially in oncologic diseases. This study was performed to evaluate the difference in the health-related quality of life following breast conserving surgery and autologous breast reconstruction after mastectomy. PATIENTS AND METHODS: Hundred and forty-four breast cancer patients were included in this study. Sixty seven patients underwent breast conserving surgery followed by radiotherapy. In 77 patients a mastectomy was performed with immediate or late reconstruction. To evaluate the health-related quality of life we used the SF-36 self-administered questionnaire. RESULTS: A significant difference was found in quality of life in the subscale "physical functioning" showing better results in the breast reconstruction group (P = 0.01). No significant difference was found in the other subscales, but there was a tendency to a better "emotional role" among the breast reconstruction patients. CONCLUSION: Our study demonstrated that autologous tissue breast reconstruction in breast cancer patients did not affect adversely the health-related quality of life compared to breast conserving therapy when the quality of life is assessed by the standardized questionnaire SF-36. In particular, the physical function is not reported to be significantly influenced negatively by the more extensive surgical therapy.

[Long-term results of the anti-emetic effectiveness of the 5-HT3 antagonist ondansetron]. / Langzeitergebnisse der antiemetischen Effektivität des 5-HT3-Antagonisten Ondansetron.

40 patients with metastatic breast cancer, under treatment with epirubicin (greater than 50 mg/m2) and cyclophosphamide (greater than 500 mg/m2), had an antiemetic therapy with Ondansetron 3 x 8 mg day, for a maximum of 10 cycles. A total of 128 treatment cycles were analysed. There was no reduction in antiemetic efficacy, regarding vomits/day and grade of nausea. 77% (31/40) had a steady or better control of vomiting during the whole treatment period. Only 23% experienced a reduction in the antiemetic efficacy in repeated therapy. 60-100% of the patients also had control of nausea (mild or none). Generally, there were no signs for a reduction of the antiemetic efficacy of Ondansetron in repeated therapy. There were neither clinically relevant side effects nor changes in laboratory values related to Ondansetron.