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M K Heatley

Publications and source records attributed to M K Heatley.

At least 55 records · Page 3Linked to original sources

Systematic review and meta-analysis in anatomic pathology: the value of nuclear DNA content in predicting progression in low grade CIN, the significance of the histological subtype on prognosis in cervical carcinoma.

Meta-analysis, though increasingly popular in clinical medicine, has not found acceptance in anatomic pathology. This paper argues that, in combination with a systematic review of the literature, meta-analysis may be usefully applied to pathological research and two examples drawn from gynaecological pathology (the value of nuclear DNA quantitation in predicting progression in low grade cervical intraepithelial neoplasia and the difference in prognosis between squamous cell carcinoma and adenocarcinoma of the cervix) are included to illustrate the methods used and to demonstrate some of the difficulties associated with these techniques.

Animals↗

The correlation between the grade of dyskaryosis on cervical smear, grade of cervical intraepithelial neoplasia (CIN) on punch biopsy and the final histological diagnosis on cone biopsies of the cervix.

This study was carried out to assess how reliably a punch biopsy of the cervix predicts the maximum grade of CIN present and whether a colposcopically directed punch biopsy is more reliable than cytology in predicting the grade of intraepithelial neoplasia present in the cervix. The grade of CIN in 107 cone biopsy specimens was compared with the grade of CIN and dyskaryosis in punch biopsies and smears from the same patients. Exact correlations were identified between the highest grade lesions on cone biopsy and those in 63% of punch biopsies and 49% of cervical smears. We conclude that punch biopsy provides a more reliable estimate of the highest grade of CIN present in a subsequent cone biopsy than cervical cytology, but nonetheless fails to give a consistent estimate of the final grade of CIN in a significant percentage of cases.

Biopsy↗

Direct sequencing of the p53 gene shows absence of mutations in endometrioid endometrial adenocarcinomas expressing p53 protein.

AIMS: To investigate the mutational status of the p53 gene (Tp53) in endometrial carcinomas expressing p53 protein by direct gene sequencing. METHODS AND RESULTS: Eighteen cases of endometrial carcinoma, selected on the basis of p53 protein expression as detected immunohistochemically by the monoclonal antibody DO7, were microdissected in the p53 positive areas. DNA was extracted and subjected to polymerase chain reaction (PCR) for exons 5-8 which code for conserved areas containing mutational hot-spots. The PCR amplified material was then sequenced using an ABI automated sequencer and analysed using BLAST software at the NCBI web site. All sequences analysed were wild-type. CONCLUSION: The results confirm that expression of p53 protein may occur in endometrial adenocarcinoma without mutation and may be due to stabilization of the protein during its normal function, possibly by an mdm2 mediated process.

Adenocarcinoma↗

In routine diagnostic practice, how many sections should we examine from cases of products of conception?

In order to determine whether a single representative section taken from routine specimens of products of conception would contain sufficient material to trigger a more comprehensive search for the features of a hydatidiform mole, cases of gestational trophoblastic disease submitted over a five year period were reviewed. Partial hydatidiform moles were either suspected or diagnosed on the first histological section in 46 (92%) cases. In the remaining four cases, although abundant placental tissue showing diagnostic features was available in later blocks, most of the tissue in the first block consisted of endometrial tissue with only occasional chorionic villi being identified. The current study shows that a molar gestation can be suspected after examining a single tissue block, providing that it contains a representative number of chorionic villi. If a molar pregnancy is suspected clinically or pathologically, additional blocks should be examined to secure the diagnosis and classify the condition.

Adult↗

What is the value of proliferation markers in the normal and neoplastic cervix?

Markers of cellular proliferation have been widely applied in cervical disease and include techniques which are applicable to routinely processed tissue including standard hematoxylin and eosin sections, and sections labelled with antibodies to Ki-67 and PCNA proteins. Flow cytometry and in vivo techniques including labelling with Bromodeoxyuridine (BrdU) and radiolabelled thymidine require more specialized facilities. Increases in the mitotic index and the Ki-67 and PCNA labelling indices, the incidence of aneuploidy together with increases in in vivo labelling with BrdU and radiolabelled thymidine have been demonstrated as the grade of cervical intraepithelial neoplasia (CIN) increases. With respect to invasive tumours increases in these parameters are associated with increased tumour size, stage and improved survival after radiotherapy. At present the major practical application of these markers appears to be in distinguishing between postmenopausal atrophy and CIN lesions on histological sections and, in combination with the Papnet system, in identifying high grade dyskaryosis on blood stained cervical smears. Future development may permit the identification of those patients whose CIN lesion will progress, and who require treatment, to be distinguished from those whose lesions will stay static or regress and who can be followed up cytologically. This promises a more rational use of health care resources. Most of the studies to date have been on small numbers of cases. Meta-analysis of existing studies and large, possibly multicentric, prospective studies are needed to elucidate the value of these markers.

Animals↗

A high apoptotic index occurs in subtypes of endometrial adenocarcinoma associated with a poor prognosis.

A study was carried out to determine the apoptotic index (AI) in cases of endometrial adenocarcinoma that are usually associated with a poor prognosis, and to identify in the AI in these cases differs from the AI's in grade I and II endometrial adenocarcinoma. The apoptotic index (defined as the percentage of morphologically identified apoptotic cells and apoptotic bodies in counting 3000 tumor cells) was calculated for five grade III endometrial adenocarcinomas of no specific type (NST), five clear cell adenocarcinomas (CCC), three high grade uterine papillary serous carcinomas (UPSC) and one undifferentiated carcinoma of the endometrium. Overall a higher mean AI (6.3%) was identified in these poor prognosis neoplasms than in 13 grade I and II endometrial adenocarcinomas (mean AI 2.7% p < 0.0001). The apoptotic index was highest in the undifferentiated carcinoma (AI = 9.7%). The mean AI for the cases of UPSC, CCC and grade III endometrioid (NST) adenocarcinomas were 7.4%, 5.9% and 5.2% respectively. There was no evidence of a statistically significant difference in the AI in these poor prognosis groups (Kruskall Wallis test p = 0.45). Although the results show that a high AI is a feature of poor prognosis endometrial carcinoma, no distinction in AI was demonstrated in the subtypes examined.

Adenocarcinoma↗

The immunophenotype of human decidua and extra-uterine decidual reactions.

Decidua associated with products of conception from intra-uterine and extra-uterine gestations and decidualized tissue from the appendix, cervix and Fallopian tube were studied using a panel of antibodies and antisera. Immunolocalization of vimentin and desmin intermediate filament proteins and of alpha-1-antitrypsin and alpha-1-antichymotrypsin was identified in most of the 43 cases studied. Placental alkaline phosphatase, beta human chorionic gonadotrophin, cytokeratin, smooth-muscle actin and leukocyte markers (CD3, CD20, CD68) were also expressed in some cases. Occasional cases reacted for CD45 and S-100 protein. Similar reaction profiles were obtained at both intra-uterine and extra-uterine sites. The results show that extra-uterine mesenchymal cells which have undergone a decidual reaction correspond closely to their counterparts in the endometrial stroma. Since positive immunostaining within decidual cells for cytokeratins, placental alkaline phosphatase and beta human chorionic gonadotrophin indicates that trophoblastic cells are not exclusively recognized by these antibodies, their use does not permit the confident diagnosis of an intra-uterine gestation.

Alkaline Phosphatase↗

Association between the apoptotic index and established prognostic parameters in endometrial adenocarcinoma.

The aim of this study was to determine if the apoptotic index can be readily determined for endometrial carcinoma in hysterectomy specimens and to establish if any association exists between the apoptotic index and tumour grade and stage. The apoptotic index, defined as the percentage of morphologically identified apoptotic cells and apoptotic bodies in 3000 tumour cells, was calculated for 15 adenocarcinomas of the endometrium. An association between apoptotic index and tumour grade and stage was sought. Two grade 3 adenocarcinomas of endometrium had a higher apoptotic index (5.15% to 6.43%) than 13 grade 1 and 2 lesions (1.18% to 3.8%) and formed a distinct group in this series. No association between apoptotic index and tumour stage was demonstrable. Apoptotic index can be readily estimated in routine hysterectomy specimens for endometrial adenocarcinoma. A high apoptotic index shows an association with features normally correlated with a poor clinical outcome although its value as an independent prognostic index has yet to be established.

Adenocarcinoma↗