Clonal p53 mutation in primary cervical cancer: Association with human-papillomavirus-negative tumours

Citations from the Literature borderline change in cervical smears. Design - Retrospective study of women undergoing routine cervical cytological screening in 1981. Setting - Avon Cervical Screening Programme, covering 250,000 women in Bristol and Weston super Mare. Subjects - 437 women showing borderline cervical changes in 1981 and 437 age matched controls with normal results in 1981. Main outcome measures - Cytological progression to high grade dyskaryosis (cervical intraepithelial neoplasia grade III or invasive carcinoma). Results - During follow up ranging from 13 to 106 months 98 of the 437 women (22.4%) with borderline cytological changes on routine cervical cytology screening had a subsequent smear test showing high grade dyskaryosis compared with three of the 437 women (0.9%) in the control group. The risk of progression was greater in women aged 20 to 39 than in those aged 40 and over. Human papillomavirus infection had initially been diagnosed cytologically in 101 of the 437 (23%) women with borderline results. Significantly fewer of these women developed high grade dyskaryosis (13/98 (13%) v 881339(26%), P < 0.05). Conclusions - Women with borderline smear test results are at increased risk of developing high grade dyskaryosis, particularly if the borderline changes occur without cytological features of human papillomavirus infection. Progression occurs within three years in 50% of cases, although a linearly increasing risk was sustained over the nine years of follow up and was greatest in women aged 20 to 39. Careful follow up of these women is indicated. CIonaI p53 motation in primary cenieal cancer: AmoeiatIon with human-papIIInmavlrus-negative turnours Crook T.; Wrede D.; Tidy J.A.; Mason W.P.; Evans D.J.; Vousden K.H. GBR LANCET 1992 339/8801 (1070-1073) Analyses of cancer cell lines and of anal cancers suggest an inverse correlation between infection with human papillomavirus (HPV) and somatic mutation of the ~53 tumour-suppressor gene. We have investigated this association in primary cervical tumours. Tumour-tissue samples from 28 women with primary cancer of the cervix were analysed for presence of HPV sequences and for somatic mutations of the ~53 gene. Southern blot analysis and the polymerase chain reaction (PCR) showed that 25 of the tumours contained HPV sequences; 20 were HPV16 positive and 5 HPVl8 positive. 17 tumours subjected to restriction fragment length polymorphism analysis for the short arm of chromosome 17 showed no evidence of allelic deletion. Sequencing of the entire coding region of the ~53 gene by asymmetric PCR detected heterozygous point mutations in only 3 HPV-negative tumours. By contrast, in 21 HPV-positive cancers of the ~53 sequence was wild-type throughout. Our data indicate that loss of wildtype p53 function is important in the pathology of cervical cancer and that in the absence of an HPV-encoded gene product that mediates loss of ~53 function, somatic mutation of the gene is required. This pattern of ~53 mutation may partly explain the apparently worse prognosis of HPV-negative cervical cancers.

359

MidmaIIy inwaive vulvar carcinoma: An h&cation for comervative mrgic8l therapy Kelley J.L. III; Burke T.W.; Tomos C.; Morris M.; Gershenson D.M.; Silva E.G.; Wharton J.T. USA GYNECOL ONCOL 1992 44/3 (240-244) It has been proposed that squamous carcinoma of the vulva with 1 mm or less of stromal invasion can be treated with local resection without inguinal node dissection. A retrospective review of 255 cases of stages I and II vulvar carcinoma demonstrated 24 cases of minimally invasive carcinoma. All cases were subjected to detailed chart review and pathologic confirmation. Mean age at diagnosis was 60 years. Seven patients had a preoperative diagnosis of preinvasive disease, ten had stage I disease and seven had stage II disease. Fifteen cases had associated vulvar carcinoma in situ. Treatment consisted of local excision in 2 patients, radical wide excision in 11, hemivulvectomy in 5 and radical vulvectomy in 6. Eleven patients had either unilateral or bilateral inguinal node dissection. Five-year life-table survival was 89%. Four patients (17%) developed recurrent dysplasia and four (17%) developed invasive recurrences. One invasive recurrence was in an inguinal node in a patient previously treated with a hemivulvectomy and negative ipsilateral superlicial node dissection. Univariate analysis revealed no statistically significant associations between recurrence and age, symptom duration, margin status, location, FIG0 stage, or coexisting VIN. Large areas of coexisting dysplasia and variable gross appearance make meaningful application of FIGG staging criteria difficult in lesions with minimal focal invasion. Wide excision or radical wide excision of lesions with ‘high-risk’ VIN or those showing 1 mm of stromal invasion on biopsy is adequate therapy. If final pathologic review demonstrates deeper invasion, a selective

Careful surveillance with, liberal use of colposcopy and biopsies is indicated in these patients. A rapid and simple method for the purification of tumor cells from ascitic fltdd of ovariao carcinoma Hirte H.W.; Clark D.A.; Mazurka J.; O’Connell G.; Rusthoven .I.

CAN GYNECOL ONCOL 1992 4413 (223-226) Rapid isolation of tumor cells growing in clumps from the ascitic fluid of patients with ovarian carcinoma was achieved by harvesting cells from ascitic fluid and subsequently passing them over a 30-m nylon mesh filter. Single cells and small cell aggregates passed through the mesh and large cell clumps that had not passed through the filter were isolated by backwashing. Morphologically, the cells in the, clumps consisted almost entirely of tumor cells. The clumps were analyzed by immunccytochemistry and only a small proportion of cells (3.1 f 0.5% to 8.3 f 0.8%) stained with anti-CD4S monoclonal antibody (a panleukocyte marker for cells of hematopoietic origin). Most of the cells in clumps stained positively (90.6 f 1.7% to 97.5 + 0.5%) with 2G3 (a monoclonal antibody binding to a high-molecular-weight Int J Gynecol Obstet 39