S.K. Lam

Prevalence and Significance of HER-2/neu Amplification in Epithelial Ovarian Cancer

Amplification of the HER-2/neu oncogene was assessed in 80 cases of epithelial ovarian tumors using differential polymerase chain reaction. HER-2/neu gene was amplified in 22 of 46 invasive cancers (48%) and in 5 of 34 borderline cancers (15%), but none of the 20 specimens of normal ovaries showed amplification. THis difference is statistically significant (p = 0.00004). The incidence of HER-2/neu amplification in late stage (III-IV, 77%) was significantly higher than that in early stage (I-II, 21%) in invasive epithelial carcinoma (p = 0.0004). There was no correlation between HER-2/neu amplification and cell type or grade of tumor. In cases of ovarian tumors of borderline malignant potential, the amplification of HER-2/neu was not correlated with clinicopathologic features. Follow-up with a mean of 22 months (6-50 months) was available for 39 cases of invasive ovarian cancers and all 34 borderline ovarian cancers. The incidence of HER-2/neu amplification in the invasive cancer and borderline cancer patients who were alive with disease was 50 and 50%, and is not statistically different from that in the patients who were alive with no evidence of disease (p = 0.662 and 0.345, respectively). The incidence of amplification in the invasive cancers of patients who died of the disease (86%) was higher than that in the patients who were still alive (44%), but the difference is not statistically significant (p = 0.175). This study supports the association of HER-2/neu amplification with progression of invasive ovarian cancer. It also suggests that HER-2/neu amplification may be an adjunctive prognostic factor of invasive epithelial ovarian cancer, shown to be associated with an unfavorable clinical course. In addition, HER-2/neu amplification occurs relatively infrequently in early invasive and borderline ovarian cancers, making it unlikely that such amplification is a general early event in ovarian carcinogenesis.

Frequent ras gene mutations in squamous cell cervical cancer

Eighty samples of cervical invasive squamous cell carcinoma were examined for ras gene mutations using polymerase chain reaction (PCR) followed by restriction enzyme digestion. We found 28 (35%) cervical cancers contained ras mutations at H-ras codon 12, 49 (61%) at K-ras codon 12, and 5 (6%) at K-ras codon 13. There were no significant differences in incidence of the ras gene mutations among different histologic grades or clinical stages of the cancer (P > 0.05). This result suggests that ras mutation may be an important step involved in a substantial number of cervical carcinoma. The interaction of ras with other genes and/or events may also be involved in pathogenesis of this malignancy.

c-fos Overexpression Is Associated with the Pathoneogenesis of Invasive Cervical Cancer

The molecular genetics of human cervical cancer remains to be defined to a significant extent. The current study examined the prevalence and significance of proto-oncogene c-fos overexpression in cervical cancer. Immunohistochemical staining of c-fos oncoprotein was performed in 27 invasive cervical carcinomas and 30 cervical intraepithelial neoplasias (CINs) managed in our department. Eight normal cervical specimens were used as controls. In the patients with invasive cervical cancer, 8 were stage I, 12 were stage II, and 7 had stage III-IV disease. Three of the cancers were well differentiated, 18 were moderately differentiated and 6 were poorly differentiated. Twenty invasive cervical carcinomas (59%) and 3 CIN (10%) showed overexpression of c-fos. The difference is statistically significant (p < 0.001). No statistically significant relationship was found between c-fos overexpression and clinical stage, histological grade, or survival in invasive cervical cancer. In this population, c-fos overexpression appears to be common in invasive cervical cancer and correlated with the ability of the tumor to become invasive, but is not associated with the progression of cervical cancer.

Transrectal ultrasound in the evaluation of cervical carcinoma and comparison with spiral computed tomography and magnetic resonance imaging

38 women with biopsy proven untreated cervical carcinoma were prospectively studied with transrectal ultrasound (TRUS), spiral computed tomography (SCT) and magnetic resonance imaging (MRI). 20 women had radical hysterectomy and pelvic lymphadenectomy with detailed histological evaluation of the parametra. The echographic features of cervical carcinoma on TRUS are a hypoechoic (60%) or isoechoic (40%) (relative to normal uterine muscle/cervical stroma), poorly defined mass lesion with indistinct margins in an enlarged cervix. This relatively high percentage of isoechoic tumours and relative lack of contrast resolution may pose a problem in the identification of some tumours, and to our knowledge has not been previously reported. Further limitations of TRUS are in the evaluation of advanced cervical cancer, due to bulky tumours rendering poor access to the parametrium and pelvic sidewall. The overall accuracy in staging of early cervical cancer (less than stage 2b) was 85% for examination under anaesthesia (EUA), 75% for TRUS, 65% for MRI and 50% for SCT. The positive predictive value in evaluating the parametra in this group of patients was also lower for SCT (14%) and MRI (33%) compared with TRUS (100%). In the evaluation of advanced cervical cancer (stage 2b or higher), there was poor correlation between TRUS and EUA, with MRI showing the best correlation with EUA. We conclude that SCT is inferior to both TRUS and MRI in the staging of early stage cervical cancer.

HER‐2/neu Gene Amplification in Cervical Cancer in Chinese Women of Hong Kong and China

Objective: To determine the amplification of proto‐oncogene HER‐2/neu in invasive cervical cancer and its relationship with the stage of disease, grade of tumor and prognosis of patients.

Gonadoblastoma in Patient with Turner's Syndrome

A 15‐year‐old phenotypic female referred for the investigation of primary ammenorrhea, was found to have a 45 XO karyotype and an ovarian cyst. She demonstrated some of the features of Turners syndrome, as well as virilization. On laparotomy, she was found to have bilateral gonadoblastomas. She was treated with total abdominal hysterectomy and bilateral salpingo‐oophorectomy. Subsequently, repeated chromosomal analysis detected the presence of Y chromosomes, which was confirmed by the use of polymerase chain reaction (PCR). The difficulties encountered in searching for the Y chromosome in patients with gonadoblastoma are discussed. Prophylactic gonadectomy is suggested in those cases associated with atypical features.

Ovarian epithelial tumour in gonadal dysgenesis. A case report and literature review.

A patient with gonadal dysgenesis was found to have a mucinous epithelial ovarian tumour on the left side and a streak gonad on the right. The preponderance of mucinous tumours (5 of 8) over other epithelial tumours in these patients is noted but the significance is not fully understood. Two models of pathogenesis (incessant ovulation and hypergonadotrophic hypogonadism) were proposed but neither satisfactorily explains the development of the tumours. Further ultrastructural, chromosomal and molecular biological study of these tumours may help to elucidate the underlying cause and pathogenesis.

Epidemiology and aetiology of trophoblastic disease

Trophoblastic disease results from an inappropriate and excessive proliferation of the trophoblast. Most cases result from an antecedent pregnancy where abnormal fertilisation has occurred. These abnormal fertilisations result in hydatidiform moles. Most, but not all cases of gestational trophoblastic disease (GTD) follow hydatidiform moles. Only maternal age, a previous molar pregnancy in the woman and race (with the co-variate of geography) have consistently been identified as epidemiological risk factors. Whilst the genetic pathogenesis of hydatidiform moles is well understood, the aetiological factors that result in these abnormal fertilisations remain unclear. It is not possible to examine the epidemiology or aetiology of non gestational trophoblastic disease adequately because of its rarity.