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Biomedical subjects

M K Heatley

Publications and source records attributed to M K Heatley.

At least 37 records · Page 2Linked to original sources

The value of immunocytochemistry in distinguishing between clear cell carcinoma of the kidney and ovary.

Renal clear cell carcinoma rarely metastasizes to the ovary potentially mimicking a primary ovarian clear cell carcinoma. The immunocytochemical profiles of the two tumors were compared. Control groups of ovarian endometrioid and serous adenocarcinomas were also examined using the same antibody panel. Paraffin sections were studied with the immunocytochemical technique using eight antibodies. Renal clear cell carcinomas were positive for vimentin (8/12 cases), CK5/6 (0/12), 34 beta E12 (1/12), Ber-Ep4 (5/12), CA125 (0/12), ER (1/12), and PGR (1/12). Ovarian clear cell carcinomas showed positivity with vimentin (1/10 cases), CK5/6 (2/10), 34 beta E12 (10/10), Ber-Ep4 (10/10), CA125 (8/10), ER (7/10), and PGR (6/10). Endometrioid adenocarcinomas were positive for vimentin (9/10 cases), CK5/6 (8/10), 34 beta E12 (10/10), Ber-Ep4 (9/10), CA125 (9/10), ER (9/10), and PGR (10/10). Eight serous adenocarcinomas were positive in all cases for all the antibodies except CK5/6 (7/8 cases) and 34 beta E12 (7/8 cases). All the tumors reacted for epithelial membrane antigen. This immunohistochemical panel allows clear cell carcinomas of kidney and ovary to be distinguished. The latter has a greater phenotypic similarity with serous and endometrioid adenocarcinomas than with renal clear cell carcinoma demonstrating yet again that these ovarian tumors share a common histogenetic origin.

Adenocarcinoma, Clear Cell↗

The appropriateness of examining the entire cervix histologically in hysterectomy specimens from women with a previous history of cervical intraepithelial neoplasia or dyskaryosis.

BACKGROUND/AIMS: To investigate the necessity of examining the entire cervix in hysterectomy specimens from women with a previous history of cervical intraepithelial neoplasia (CIN) or dyskaryosis. METHODS: The overall frequency with which squamous CIN was encountered in hysterectomy specimens of women with a previous diagnosis of squamous CIN or dyskaryosis was calculated in a sample of 71 women. The frequencies in women with positive or negative smears or biopsies between the initial diagnosis and hysterectomy, and in women with no intervening smear or biopsy, were also estimated. RESULTS: A persistent CIN lesion was identified in 18 patients (13 high grade cases; five low grade cases). A further eight patients who had high grade CIN also had microinvasive disease (seven cases of FIGO stage 1a1; one case of FIGO stage 1a2). Ten of the 20 patients with a positive smear or biopsy, but none of the 16 patients with a negative smear or biopsy between initial diagnosis and hysterectomy, had an abnormality on the hysterectomy specimen. Sixteen of the 35 patients who did not have an interim smear or biopsy had CIN in the hysterectomy cervix. CONCLUSIONS: These results support continuing the practice of examining the entire cervix in hysterectomy specimens from women with a previous cervical abnormality, regardless of its histological or cytological grade, if there has been a positive interim smear or biopsy or if neither investigation has been performed.

Biopsy↗

Florid cystic endosalpingiosis of the uterus.

A 73 year old woman presented with a right sided adnexal cystic mass. At laparotomy, this proved to be a benign serous ovarian cyst and an aggregation of thin walled subserosal and soft tissue cysts and spongy nodules up to 16 mm in diameter involving the side wall of the uterus and adjacent parametrium. These were removed by total abdominal hysterectomy and bilateral salpingo-oophorectomy. Histologically, the cystic spaces and smaller acini were lined by benign tubo-endometrioid epithelium, with smaller areas typical of serous differentiation and rare microfoci of endocervical-type mucinous epithelium. These features indicated multidirectional Mullerian differentiation in a process that, overall, was consistent with so called florid cystic endosalpingiosis. This lesion is to be distinguished from other benign conditions including multicystic mesothelioma, endometriosis, endocervicosis, florid deep glands of the uterine cervix, and deep Nabothian cysts of the uterine cervix.

Aged↗

The prognosis in cervical epithelial changes of uncertain significance is similar to that of cervical intraepithelial neoplasia grade 1.

BACKGROUND/AIMS: The term epithelial changes of uncertain significance (ECUS) describes a minor degree of nuclear pleomorphism limited to the basal layers of cervical epithelium in the absence of severe inflammation with associated normal mitoses, koilocytosis, or koilocytosis associated features. This study aimed to investigate the long term prognosis of this lesion. METHODS: Slides from 128 women with low grade cervical abnormalities, accessioned consecutively, were reviewed. RESULTS: In 43 women the initial diagnosis of ECUS was confirmed and in 30 women the initial diagnosis of cervical intraepithelial neoplasia grade 1 (CIN1) was confirmed. Comparison of follow up data from these 73 women revealed a similar prognosis in the two groups in terms of regression to normal, persistence of low grade disease, or progression to high grade CIN. CONCLUSIONS: Low grade cervical disease (ECUS and CIN1) should be managed according to similar treatment protocols.

Disease Progression↗

How many histological levels should be examined from tissue blocks originating in cone biopsy and large loop excision of the transformation zone specimens of cervix?

AIMS: To establish the value of examining additional histological levels in cone biopsy and large loop excision of the transformation zone (LLETZ) specimens of cervix. METHODS: Three deeper levels were examined from 200 consecutive cone biopsy and LLETZ specimens reported by a single pathologist. RESULTS: Examination of the first deeper level resulted in cervical intraepithelial neoplasia (CIN) being identified for the first time in five cases and in CIN1 being upgraded in five more. Invasive cancer was discovered in two cases that had shown high grade CIN initially. CONCLUSION: Examination of a single further level appears to be sufficient in those patients in whom a specimen is compromised because epithelium including the squamocolumnar junction is missing, or if there is a discrepancy between the histological findings and the preceding colposcopic or cytological history. If invasive disease is suspected on the basis of the cytological, colposcopic, or histological features, one or preferably two further levels should be examined.

Biopsy↗

Structural and cell surface antigen expression in the rete ovarii and epoophoron differs from that in the Fallopian tube and in endometriosis.

AIMS: We compared the immunohistochemical profiles of the rete ovarii and endometriosis in order to identify a panel which distinguishes between these structures. The immune profiles of the epoophoron, Fallopian tube and ovarian surface epithelium were also studied. MATERIALS AND METHODS: Twenty-four women with no evidence of endometriosis and seven who had endometriosis in the uterine adnexae were studied using nine antibodies to intermediate filament proteins and cell surface markers. None of the structures studied shared an identical profile of immunohistochemical reaction. The immunoprofile of endometriosis showed some similarities to that of the Fallopian tube, but differed from that of the rete ovarii, epoophoron and ovarian surface epithelium CONCLUSIONS: A panel including Ca-125, epithelial membrane antigen and the epithelial glycoprotein BerEp4 would permit the distinction between endometriosis and the rete ovarii in problematic cases. The study showed some commonality in reaction between endometriosis and the Fallopian tube which indicates that they may share a common (paramesonephric) origin. There was little commonality in the immunoprofile of endometriosis and the ovarian surface epithelium implying that endometriosis is unlikely to develop as a result of serosal metaplasia.

Antigens, Surface↗

Systematic review and meta-analysis in anatomic pathology.

Systematic reviews and meta-analyses are techniques of data retrieval and analysis which complement traditional narrative reviews. They are widely used in clinical medicine and are finding an increasing role in anatomical pathology. Performing high quality systematic review and meta-analysis requires the accumulation of large numbers of cases from well planned and executed studies and is facilitated if data is presented in a standardized manner. Techniques which allow data from individual patients included in a variety of different studies are now being developed indicating that in future research papers may require a more detailed description of results than in the past. This need may be met by posting anonymised data on the Internet. Systematic reviews and meta-analyses are never complete since data are continually contributed and analyses constantly updated. As with any research paper, the results of these techniques require careful evaluation and the role of the expert reviewer is enlarged by these methodologies.

Humans↗

An immunohistochemical study of the rete ovarii and epoophoron.

A study to compare the immuno-histochemical profile of the human rete ovarii, and epoophoron, with the Fallopian tube and ovarian surface epithelium was performed with 31 antibodies and antisera. A reaction was present in the epithelial cytoplasm of the rete ovarii and epoophoron of mesonephric origin, for vimentin, GFAP, cytokeratin markers, (AE1/AE3, MNF116; Cam 5.2, 34 beta E12 and for the monospecific antibodies to cytokeratins 7 and 19), heat shock protein 27, in the cell membrane for HBME-1, EMA and in the subepithelial collagen for collagen IV. Reactions were present only in the epithelium in the rete ovarii for EGFR (one case) and CA-125 (four cases). A reaction was present in the epithelium of the epoophoron only for Ber-EP-4 and S100. There was no reaction with antibodies for desmin, neurofilament protein, cytokeratins 20 or 14, actin, calretinin, E-cadherin, C-erb-B2, or CEA (monoclonal and polyclonal reagents). The immuno-histochemical profile of the Fallopian tube was consistent with its para-mesonephric origin and that in the ovarian surface epithelium was consistent with a proposed modified mesothelial origin. This study provides an immunohistochemical profile of these structures with a large panel of commonly available antibodies and antisera, confirming and extending the findings described in previous studies.

Antigens, Surface↗

p53 expression, p21 expression and the apoptotic index in endometrioid endometrial adenocarcinoma.

AIMS: Although several genetic abnormalities are known to occur in endometrial cancer, including tp53 gene mutation, the pathogenesis of this common malignancy remains poorly defined. We investigated the relationship between overexpression of p53 protein, p21 protein expression and apoptosis in endometrial carcinoma. METHODS AND RESULTS: Sixteen cases of endometrial carcinoma in which polymerase chain reaction analysis had demonstrated the absence of a tp53 gene mutation were selected on the basis of p53 protein expression; p21 protein expression and the apoptotic index were then determined for each case. The proportion of cells in each case expressing p53 and p21 protein immunoreactivity was compared with the apoptotic index. Overall, no significant correlation was demonstrated between p53 and p21 immunoreactivity, or between either p53 or p21 and the apoptotic index. CONCLUSIONS: Factors other than p53 are involved in the regulation of p21 expression and apoptosis in endometrioid endometrial adenocarcinomas without p53 mutations. Despite the small numbers used in this study, the data suggest a correlation between low levels of p53 immunoreactivity and apoptosis. We postulate that high levels of p53 immunoreactivity may be due to abnormal stabilization of the p53 protein. Follow-up studies are needed with a larger data set.

Aged↗

The expression of the proliferation marker Ki-67 and oestrogen and progesterone receptors in the proximal and distal fallopian tube.

Significant epithelial proliferation is identified more frequently in the fallopian tube in patients with ovarian tumours than in control patients. More extensive sampling of the fallopian tube is also associated with a more frequent identification of epithelial proliferation. We compared cellular proliferation at either end of the fallopian tube as detected with an antiserum to the Ki-67 protein. Variations in oestrogen and progesterone receptor proteins were also examined. Proliferative activity as expressed by the Ki-67 protein, and oestrogen receptor expression was greater in the proximal fallopian tube and progesterone receptor expression was greater in the distal fallopian tube. Only the difference in progesterone receptor expression was statistically significant (P =0.0431). This study indicates that variations in Ki-67, oestrogen and progesterone receptor protein expression occur at different sites in the fallopian tube. This should be taken into account when planning studies of epithelial cell proliferation in the fallopian tube in the future.

Journal Article↗

Follow up of women with borderline cervical smears as defined by national guidelines.

AIM: To determine the proportion of women with abnormalities in cervical smears corresponding to borderline nuclear change, as defined by national guidelines, which return to normal or persist as cytological or histological abnormalities. METHODS: 313 women with borderline nuclear change diagnosed by a single pathologist using the national criteria were followed up for up to two years. RESULTS: On initial follow up, 45% of women had a negative smear or biopsy, 46.5% had a low grade cytological or histological abnormality, and 8.5% had a high grade abnormality. Of 81 patients in whom a second follow up smear or biopsy was available, 47% had no detectable abnormality, 38.5% had low grade lesion, and 14.5% had a high grade lesion. In total, 32 patients (10.2%) had a high grade lesion (defined as moderate or severe dyskaryosis on smear or CINII or CINIII on biopsy) on at least one follow up sample. CONCLUSIONS: The results support the use of the national criteria defining borderline nuclear change in identifying women at increased risk of developing a high grade cervical intraepithelial neoplasia, as identified histologically or cytologically, and highlight the importance of follow up in these patients.

Cervix Uteri↗

A comparison of three methods of orienting cervical punch biopsies.

AIMS: To compare methods of orienting cervical punch biopsies, since well oriented biopsies are needed to optimise the diagnosis and grading of cervical intraepithelial neoplasia. METHODS: The orientation, the presence and preservation of the squamocolumnar junction, and the presence or absence of the surface layers of the squamous epithelium were compared in 345 cervical biopsies that had either been attached to paper (n = 112), floated directly into 10% formalin (n = 107), or floated into a solution of 10% formalin including 0.05% eosin (n = 126) in the colposcopy clinic. RESULTS: When the specimens were mounted on filter paper before fixation, they were more likely to be optimally oriented, to have a preserved squamocolumnar junction, and to have intact surface epithelium than specimens that were handled using the other methods, even when the specimens floated off the paper in transit. CONCLUSIONS: Cervical biopsy specimens should be mounted on paper before fixation and submission to the laboratory.

Biopsy↗

Ki-67, oestrogen receptor, and progesterone receptor proteins in the human rete ovarii and in endometriosis.

AIM: To examine proliferative activity using the Ki-67 protein, oestrogen receptor protein, and progesterone receptor protein expression in the rete ovarii, and to make comparisons with their expression in endometriosis. METHODS: Immunohistochemistry was used to study the rete ovarii in 24 cases and endometriosis in seven cases, using antibodies to Ki-67 protein (growth fraction (GF) quantified using a point score method) and oestrogen receptor and progesterone receptor (quantified using the H score method). RESULTS: There was no evidence of a significant difference in the Ki-67 protein, oestrogen receptor, and progesterone receptor in the rete ovarii in different phases of the menstrual cycle (proliferative phase: GF = 1.052, oestrogen receptor H score = 13.4, progesterone receptor H score = 15.32; secretory phase: GF = 0.736, oestrogen receptor H score = 7.5, progesterone receptor H score = 1.84). The expression of all three proteins was greater in the foci of endometriosis (GF = 6.99, oestrogen receptor H score = 152.02, progesterone receptor H score = 127.36) than in the rete ovarii (p < 0.0005-0.0008, Mann-Whitney U test). CONCLUSIONS: There is a low rate of cellular proliferation in the rete ovarii and this structure shows less responsiveness to hormone stimulation than foci of endometriosis. These differences may provide a useful tool to distinguish the rete ovarii from endometriosis in cases of diagnostic difficulty.

Endometriosis↗