Danny K.L. Cheng

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.

Metastatic trophoblastic disease after an initial diagnosis of partial hydatidiform mole: genotyping and chromosome in situ hybridization analysis.

Hydatidiform mole (HM) is classified into partial (PHM) and complete (CHM) subtypes according to histopathologic and genetic criteria. Traditionally, it is believed that PHM carries a better prognosis and rarely develops metastasis. However, making a distinction between PHM and CHM using histologic criteria alone may be difficult.

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.

The behaviors of seeking a second opinion from other health-care professionals and the utilization of complementary and alternative medicine in gynecologic cancer patients

Goals of workThe aim of the study is to determine the predictors for seeking a second opinion and the utilization of complementary and alternative medicine (CAM) among gynecologic cancer patients.Patients and methodsPatients attending a gynecologic cancer clinic of a tertiary referral center were recruited over a period of 1 year. A survey was conducted for all the participants in a one-on-one basis.Main resultsOne hundred ninety-one patients were recruited. Eighty patients (41.9%) had consulted other health-care professionals (HCP) for a second opinion after they were diagnosed to have cancer and 89 (46.6%) had utilized CAM. In multivariate analysis, late-stage disease (OR=2.65, 95% CI 1.26–5.58), treatment with radiotherapy (OR=2.27, 95% CI 1.19–4.33) and tertiary education (OR=11.28, 95% CI 3.06–41.54) were independent predictors for seeking a second opinion from other HCP and utilization of CAM. Patients who sought a second opinion from other HCP were more likely to utilize CAM (OR=6.12, 95% CI 3.24–11.54). Eighty percent of the patients did not inform their usual caregiver their utilization of CAM.ConclusionsSeeking a second opinion from other HCP is common in gynecologic cancer patients. Patients who seek a second opinion are more likely to utilize CAM.

Tumour markers and their prognostic value in adenocarcinoma of the cervix

Ninety-one patients with adenocarcinoma of the cervix had 4 tumour markers (TMs) assayed before treatment. Serum squamous cell carcinoma antigen (SCC) (n = 91) was raised in 25%; tissue polypeptide antigen (TPA) (n = 78) was raised in 35%; carcinoembryonic antigen (CEA) (n = 34) was raised in 26% and CA 125 (n = 64) was raised in 27% of these patients. In 47 of these 91 patients (52%), 1 or more of the markers were raised. The percentage of patients with raised TM increased with advancing stage. Univariate survival analysis showed that age, stage, raised TPA, raised CA 125, and raised TMs (any one or more) were of prognostic significance. When multivariate analysis was done and each TM was individually analysed, only age, stage and raised CA 125 were of prognostic significance. Rising SCC or TPA or CA 125 levels in serial estimations correlated well with the occurrence of recurrence. Thus, pretreatment estimation of SCC, TPA and CA 125 can be used to identify the patients who can subsequently be monitored by serial TM estimation.

Homozygous Arginine at Codon 72 of p53 Has No Prognostic Significance in Cervical Cancer

Mutation of p53, a tumour suppressor gene, is uncommon in cervical cancer but the detection of human papillomavirus (HPV) DNA in cervical cancer is common. The findings of increased susceptibility to degradation of p53 by E6 protein of HPV16/18 in cervical cancer with homozygous arginine at codon 72 (HA72) of p53 led to this study on whether cervical cancers with HA72 were more aggressive with the increase in the rate of loss of p53 function. In 102 cervical cancers, 76.5% were HPV16/18 positive and 30% had HA72. No survival difference was detected between HA72 and non-HA72 tumours irrespective of HPV16/18 status. Furthermore, the detection of HPV16/18 in cervical cancer was found not to be of prognostic significance in this study.

Clinicopathologic study of 16 cases of primary tubal malignancy.

Sixteen cases of primary carcinoma of the fallopian tube were diagnosed and treated at Queen Mary Hospital, Hong Kong from July 1972 to June 1992 constituting 0.26% of the total gynecologic malignancies seen during that period. The average age was 61 years and the most common presenting symptom was abnormal vaginal bleeding. Preoperative diagnosis is difficult; in only one case was a diagnosis of malignancy made by cervical smear. An adnexal mass was detected in 13 of the cases (81.3%) either by clinical examination and/or ultrasonography. Therapy consisted of surgical resection, usually followed by various combinations of adjuvant radiation therapy and chemotherapy. The cumulative survival was 62%. In addition to the typical form of adenocarcinoma, one case of squamous cell carcinoma and a case of multifocal endometrioid adenocarcinoma were observed. One case of an apparently usual form of adenocarcinoma recurred as a heterologous malignant mixed Müllerian tumor 2 years after diagnosis. This series further emphasises the wide range of differentiation possible in the Müllerian system and the variety of neoplasms which may arise from it.