L.C. Wong

Chemoradiation and Adjuvant Chemotherapy in Cervical Cancer

PURPOSE Radiotherapy is the standard treatment for locally advanced cervical cancer, but treatment results remain disappointing, particularly for women with bulky central disease. We investigated the role of concurrent chemoradiation and adjuvant chemotherapy in a randomized trial. PATIENTS AND METHODS Two hundred twenty patients with bulky stage I, II, and III cervical cancer were randomized to receive either standard pelvic radiotherapy or chemoradiation (epirubicin 60 mg/m(2)) followed by adjuvant chemotherapy with epirubicin 90 mg/m(2) administered at 4-week intervals for five additional cycles. RESULTS Fifty-nine patients have relapsed, with a median follow-up duration of 77 months. Patients who received epirubicin radiation therapy showed a significantly longer disease-free (P =.03) and cumulative survival (P =.04). Patients who received radiation alone had significantly more distant metastasis than those who received chemoradiation (P =.012). There was no difference in long-term local tumor control (P =.99). CONCLUSION Survival benefit has been demonstrated in patients treated with chemoradiation followed by adjuvant chemotherapy with epirubicin as compared with patients treated with standard pelvic radiotherapy alone.

E-cadherin expression is silenced by DNA methylation in cervical cancer cell lines and tumours

A previous study showed E-cadherin expression was lost in some cervical cancer cell lines and tumours. This study was designed to clarify the significance of DNA methylation in silencing E-cadherin expression. We examined promoter methylation of E-cadherin in five cervical cancer cell lines and 20 cervical cancer tissues using methylation-specific PCR (MSP) and bisulphite DNA sequencing. The correlation of E-cadherin methylation and expression together with methyltransferase (DNMT1) were further studied. We found that hypermethylation of E-cadherin was involved in five cervical cancer cell lines and 40% (8/20) of cervical cancer tissues. E-cadherin protein was lost in 6/8 (75%) samples and 3/5 (60%) cell lines with promoter methylation. E-cadherin methylation was significantly correlated with increased DNMT1. Using an antisense DNMT1 oligo to transfect into SiHa HeLa C33A cell line, E-cadherin protein was re-expressed. We concluded that loss of E-cadherin expression was in part correlated with DNA methylation and DNMT1 expression in cervical cancer.

Long-term follow-up of potentiation of radiotherapy by cis-platinum in advanced cervical cancer

Between January 1982 and January 1983 all patients with advanced cervical cancer were randomized into three groups: radiotherapy only (group I), radiotherapy plus weekly cis-platinum (group II), and radiation plus twice-weekly cis-platinum (group III). Better initial central control was observed in group III patients. Long-term survival was similar in the three groups. Potentiation of radiotherapy with cis-platinum failed to show any significant improvement in long-term survival.

Anti-apoptotic proteins, apoptotic and proliferative parameters and their prognostic significance in cervical carcinoma

The inhibitor of apoptosis proteins (IAP) suppress apoptosis induced by a variety of stimuli. The aims of this study were to: (a) compare the expression of X-linked IAP (Xiap) and Human IAP-2 (Hiap-2) in cervical carcinoma cells and normal cervix, (b) determine the correlation between IAP expression and tumour apoptosis or proliferation, and (c) assess their prognostic significance in cervical carcinomas. Paraffin-embedded tissue sections were retrieved from 77 patients with cervical squamous carcinomas prior to treatments and 47 normal subjects. Tumour apoptosis was determined by terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuracil triphosphate (dUTP) nick-end labelling (TUNEL) and apoptotic index (AI), and the proliferative rate was measured by Ki-67 and mitotic (MI) indices. Immunoreactive Xiap and Hiap-2 were found in both cervical cancer cells and normal tissues. IAP expressions in cancers did not correlate with apoptotic and proliferative parameters, disease stage and patient survival. The lower AI and Ki-67 index were associated with a better survival. In conclusion, the basal expression levels of IAPs have no prognostic significance, but AI and Ki-67 expression are potential prognostic indicators in cervical carcinoma.

Abnormal expression of epidermal growth factor receptor and c-erbB2 in squamous cell carcinoma of the cervix: correlation with human papillomavirus and prognosis.

The aim of this study is to assess the expression of epidermal growth factor receptor (EGFR) and c-erbB2 and their correlation with human papillomavirus (HPV) status and prognosis in squamous cell carcinoma of the cervix. The expression of EGFR and c-erbB2 was studied at the protein level using the immunohistochemical (IHC) staining method, at the RNA level using the ribonuclease protection assay and at the DNA level using Southern blot and hybridization method. One hundred and one patients with squamous cell carcinoma of the cervix were recruited. Fifty-one patients were of stage 1B/2A and 50 patients were of stage 2B and above. Positive IHC stainings of EGFR and c-erbB2 proteins were found in 74.2 and 19.8% of cases, respectively. DNA amplifications of EGFR and c-erbB2 genes were detected in 35.4 and 17.2%, respectively. Of the patients showing positive EGFR and c-erbB2 staining, only 39.2 and 25%, respectively, showed DNA amplifications. RNA overexpression of EGFR or c-erbB2 was only detected in 2% of cervical cancers and was associated with positive staining and DNA amplifications. HPV was detected in 79.2% of the cases by HPV consensus primers L1, in 57.4% for HPV 16 and 27.7% for HPV 18. The abnormal expression of EGFR and c-erbB2 had no correlation with HPV detection and had no prognostic significance on survival.

Potentiation of radiotherapy by Cis-dichlorodiammine platinum (II) in advanced cervical carcinoma

Forty-five patients with Stages II and III cervical carcinoma were randomized to receive either radiation or cis-dichlorodiammine platinum (II) (cis-DPP) with radiation. Cis-DPP was administered in bolus injections of 25 mg/m2 at weekly intervals until completion of radium application. Complete response was noted in 11/20 (55%) patients in the radiochemotherapy group compared to 5/25 (20%) patients in the radiation group (P less than 0.025). No enhanced toxicities were observed with the addition of cis-DPP to radiation. The combined use of cis-DPP and radiotherapy offers promising potential in improving local-regional control of advanced cervical carcinoma.

Methotrexate with citrovorum factor rescue in gestational trophoblastic disease.

Thirty-three patients with gestational trophoblastic disease treated with methotrexate alone and 68 similar patients treated with methotrexate and citrovorum factor rescue were analyzed. Both groups showed a comparable sustained biochemical remission rate. The group treated with methotrexate and citrovorum factor however showed a shorter interval to induction of remission (p less than 0.05). Contrary to previous reports, the methotrexate and citrovorum factor regimen failed to protect the patients against the development of hepatic toxicity, the incidence of hepatic toxicity being significantly higher in the group treated with methotrexate and citrovorum factor.

Serum squamous cell carcinoma antigen in the monitoring of radiotherapy treatment response in carcinoma of the cervix

In this study, squamous cell carcinoma antigen (SCC) was detected in 96 of 157 patients with squamous cell carcinoma of the cervix and the percentage of patients with raised SCC levels increased with the stage of disease (P less than 0.01). The use of serial SCC assays and cervical biopsy histology during the course of radiotherapy to predict tumor response to irradiation was assessed. In patients who were given external irradiation before intracavitary radium, a high SCC level or the presence of viable tumor cells in the biopsy was found to be of no predictive value. However, at completion of radiotherapy, i.e., after intracavitary radium application, patients with persistently high SCC levels had a significantly higher incidence of residual tumor than patients whose SCC levels returned to normal (P less than 0.01). In 60% of patients with a persistently high SCC level, viable tumor was found in the cervical biopsy at the end of radiotherapy. On the other hand, only 5.4% of patients whose SCC level returned to normal had residual tumor.

Primary mixed neuroendocrine and mucinous carcinoma of the ovary

SummaryA rare case of mixed carcinoma of ovary with a predominant malignant neuroendocrine and a lesser mucinous tumor component is described. Extensive areas of enteric-type epithelium containing endocrine cells were present in both the mucinous borderline tumor element and in the small foci of mucinous adenocarcinoma. Transition from the mucinous tumor to the malignant neuroendocrine component provides evidence for the derivation of some neuroendocrine or carcinoid tumors direct from mucinous tumors without necessarily being a component of a teratoma. Contrary to reported examples of mucinous carcinoid, the overgrowth and spread of the neuroendocrine component characterised the aggressive and lethal nature of this tumor.

Prognostic significance of tumour markers in endometrial cancer

Serum cancer antigen (CA) 125, CA15.3, CA19.9, carcinoembryonic antigen and tissue polypeptide antigen were analyzed in 100 normal subjects, 47 patients with benign gynaecological diseases and 97 patients with endometrial cancer. The incidence of individual elevated tumour markers (> 2SD) was 21.5-30.9% in cancer patients. Elevations of CA125 and CA15.3 were significantly associated with poor prognostic clinical factors. Univariate anaylses showed that elevated CA125, CA15.3 and CA19.9 were significantly associated with shorter survival. In multivariate analysis, CA15.3 was highly significant and had a larger hazard ratio. In conclusion, CA15.3 is a useful marker for the prognosis of patients with endometrial cancer.