Paul Cross

Prognostic significance of lymph node variables in squamous cell carcinoma of the vulva.

Background. In patients with squamous cell carcinoma of the vulva, lymph nodal, surgicopathologic variables have been studied rarely, although lymph node status is by far the most important prognostic factor. This study was designed to investigate surgicopathologic variables of lymph node metastases to evaluate their prognostic significance.

Laparoscopic assisted radical vaginal hysterectomy versus radical abdominal hysterectomy—a randomised phase II trial: perioperative outcomes and surgicopathological measurements

Please cite this paper as: Naik R, Jackson K, Lopes A, Cross P, Henry J. Laparoscopic assisted radical vaginal hysterectomy versus radical abdominal hysterectomy—a randomised phase II trial: perioperative outcomes and surgicopathological measurements. BJOG 2010; DOI: 10.1111/j.1471‐0528.2010.02479.x.

Thrombocytosis as a prognostic factor in women with cervical cancer

Background. Thrombocytosis (a platelet count >400 × 109/I) is found frequently in association with malignant disease and recently has been suggested to be a poor prognostic indicator in patients with cervical cancer. The authors decided to see if these findings could be verified.

Small volume stage 1B1 cervical cancer: Is radical surgery still necessary?

OBJECTIVE Current surgical treatment of FIGO stage 1B1 cervical cancer is radical surgery. However, several reports have shown that for small tumours a more conservative approach can be as effective in terms of survival, whilst at the same time reducing the morbidity associated with removing the parametrium. The objective of our study was to report survival and obstetric outcomes following conservative management of small-volume stage 1B1 disease. METHODS All patients with FIGO stage 1B1 cancer and estimated tumour volume of less than 500 mm(3) in a loop biopsy specimen were included in the study, irrespective of other histological characteristics. A second loop biopsy was performed to rule out residual disease in 79% of patients. RESULTS Sixty two women were identified with a median age of 35 years (range 27-67). Median tumour length was 9.75 mm (7.2-20) and median depth of invasion was 1.55 mm (0.3-5). Thirty five women (56.4%) were treated with loop biopsy, whilst 27 (45.6%) had simple hysterectomy. Fifty seven women (92%) had pelvic lymphadenectomy and one positive node was recorded. After a median follow up of 56 months (16-132) no recurrence was noted. Seven full term pregnancies have been achieved. There were no preterm deliveries or mid-term miscarriages. CONCLUSION Cervical loop biopsy or simple hysterectomy combined with negative pelvic lymphadenectomy for small-volume stage 1B1 cervical cancer offers excellent prognosis in terms of survival. Postoperative morbidity is reduced and obstetric outcomes may be improved. Should these results be verified by further prospective studies, radical surgery for these women may be avoided.

Androgen receptor expression is a biological marker for androgen sensitivity in high grade serous epithelial ovarian cancer.

OBJECTIVES In the present study we explore the effects of androgens and anti-androgens on primary cultures of EOC cells. We also investigate the effects of chemotherapy on AR expression. Epithelial ovarian cancer (EOC) arises from ovarian surface epithelial cells (OSE), which express the androgen receptor (AR). Androgen stimulation of OSE cells results in increased proliferation and protection from apoptosis. Nevertheless, in clinical trials anti-androgens have had a low objective response rate in relapsed ovarian cancer. METHODS 1. Androgen receptor (AR) expression and response to androgenic stimulation were correlated in primary ovarian cancer cells derived from ascitic fluid from patients with advanced ovarian cancer, 2. AR expression in primary epithelial ovarian cancer was investigated before and after chemotherapy using paired histological samples which had been incorporated into a tissue microarray. RESULTS Eleven primary ovarian cancer cultures were established from ascitic fluid. There was wide variation of expression of androgen receptor mRNA between cultures. Cell division increased after dihydro-testosterone (DHT) stimulation in 6 out of 11 primary cultures. The fraction of cells in S-phase increased from 4.4% in cells grown in serum-free medium to 8.3% in cells stimulated with 100 nM of DHT (P<0.001). The increase in S-phase fraction was abrogated after treatment with the anti-androgen, bicalutamide in 4 out of 5 responsive cultures. There was a strong correlation (r(2)=0.7) between nuclear AR expression by immunohistochemistry and S-phase fraction changes in primary cultures. Paired pre- and post-chemotherapy histological samples from 29 patients were incorporated into a tissue microarray (TMA). Nuclear and cytoplasmic AR expression by immunohistochemistry (IHC) decreased significantly after chemotherapy (P<0.01). CONCLUSION AR expression correlates with increased S-phase fraction in response to androgenic stimulation. Immunohistochemical analysis of AR expression needs to be further tested in clinical trials to select AR positive EOC for anti-androgen therapy. Anti-androgen use early in the course of ovarian cancer is more likely to be effective as these data suggest that androgen receptor expression decreases with exposure to chemotherapy and this may explain the low response rates seen in clinical trials of patients heavily pre-treated with multiple courses of chemotherapy.

Expression of gonadotrophin releasing hormone receptor I is a favorable prognostic factor in epithelial ovarian cancer

The majority of epithelial ovarian cancers originate in the ovarian surface epithelium. The ovarian surface epithelium is a hormonally responsive tissue, and hormones are thought to play a key role in the development of this type of cancer. Gonadotrophin releasing hormone II is one of 2 isoforms which are thought to act through gonadotrophin releasing hormone receptor I, and gonadotrophin releasing hormone II has been shown to cause growth inhibition of cultured ovarian surface epithelium. The aim of this study was to investigate the expression levels and prognostic significance of gonadotrophin releasing hormone II and the gonadotrophin releasing hormone receptor I in epithelial ovarian cancer. Gonadotrophin releasing hormone II and gonadotrophin releasing hormone receptor I messenger RNA expression was examined in 23 cancers and 7 normal ovarian surface epithelium samples by quantitative real time polymerase chain reaction. An ovarian cancer tissue microarray containing 139 cases was constructed and immunohistochemical analysis of gonadotrophin releasing hormone II and gonadotrophin releasing hormone receptor I protein expression was performed and correlated with clinical outcome data. Gonadotrophin releasing hormone II messenger RNA expression was lower in cancer samples compared to normal ovarian surface epithelium samples (P < .05). Gonadotrophin releasing hormone II protein expression correlated with histologic subtype (25% serous versus 45% nonserous, P < .05) but not with overall survival. Gonadotrophin releasing hormone receptor I messenger RNA expression was highest in serous tumors when compared to non serous (P < .05) and normal tissue (P < .001). Expression of the gonadotrophin releasing hormone receptor I protein was also found to correlate with patient survival (P < .05). We have demonstrated gonadotrophin releasing hormone II and its receptor, gonadotrophin releasing hormone receptor I, are present in clinical ovarian samples, and that gonadotrophin releasing hormone receptor I protein expression is a favorable prognostic factor, suggesting these proteins play an important role in the development of epithelial ovarian cancer.

Conservative surgical management of small‐volume stage IB1 cervical cancer

Objective  To determine outcomes of women with small‐volume stage IB1 disease managed by conservative surgical treatment.

The hormonal receptor status of uterine carcinosarcomas (mixed müllerian tumours): an immunohistochemical study.

AIM: To investigate the role of oestrogen and progesterone receptor status in uterine carcinosarcomas (mixed Müllerian tumours) to see whether the receptors were identifiable, and if so whether they were of significance clinically. METHODS: 11 cases of uterine carcinosarcoma were identified from clinical and pathology records. An immunohistochemical method was used to demonstrate oestrogen and progesterone hormone receptors on paraffin embedded material, with suitable tissue controls, staining being recorded. RESULTS: 10 of 11 cases showed staining for one or both hormone receptors in normal tissue adjacent to tumour. In four carcinosarcoma cases, staining for one or both receptors was shown within the epithelial component (appearing to correlate with the degree of epithelial differentiation); two of these cases had staining within sarcomatous areas. Two of the three patients still alive had epithelial hormone receptor positivity. CONCLUSIONS: Receptors for oestrogen and progesterone were found in four of 11 cases of uterine carcinosarcoma, using paraffin embedded material. There may be an association between hormone receptor positivity and clinical outcome.

The effect of epithelial and stromal tumor components on FIGO stages III and IV ovarian carcinosarcomas treated with primary surgery and chemotherapy

The aim of this study is to assess the effect of epithelial and stromal tumor components on survival outcomes in FIGO stage III or IV ovarian carcinosarcomas (OCS) treated with primary surgery and adjuvant chemotherapy at the Northern Gynaecological Oncology Centre (NGOC), Gateshead. Women were identified from the histopathology/NGOC databases. Age, FIGO stage, details of histology, treatment, and overall survival were recorded. Of 34 cases (1994–2006, all FIGO stages), 17 were treated with primary surgery followed by adjuvant chemotherapy for FIGO stage III or IV. The median age was 66 years (52–85 years). Cytoreduction was optimal (n= 9) or complete (n= 1) in 10/17 (59%) cases. Epithelial predominant (EP) or stromal predominant (SP) tumor (defined as >50% of either component in the primary tumor) was noted in 12 and 5 cases, respectively. Epithelial types included serous (n= 9), endometrioid (n= 5), and mixed types (n= 3). Twelve women have died of disease. The median overall survival was 11.0 months (3–74 months). On univariate analysis, survival was not affected by optimal/suboptimal debulking, platinum/doxorubicin-containing chemotherapy, or homologous/heterologous stromal components. Stromal components (>25%) adversely affected survival (P= 0.02), and there was a trend to worse survival with serous compared with nonserous epithelial components (P= 0.07). Cox regression (multivariate analysis) showed that SP tumors (P= 0.04), suboptimal debulking (P= 0.01), age (P= 0.01), and tumors with serous epithelial component (P= 0.05) were adverse independent prognostic factors. Type of chemotherapy and homologous/heterologous components (P= 0.24) did not affect overall survival. In conclusion, our study suggests that SP-OCS have a worse survival outcome than EP tumors. Tumors with serous epithelial components adversely affected the survival compared with nonserous components. Larger studies are required to confirm these effects and to identify the optimum chemotherapy regimen for OCS.

High‐grade vaginal intraepithelial neoplasia: can we be selective about who we treat?

To determine the role of conservative management in high‐grade vaginal intraepithelial neoplasia (HG VaIN).