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Biomedical subjects

A J Tiltman

Publications and source records attributed to A J Tiltman.

At least 19 recordsLinked to original sources
PubMed2005

The pathology of cervical tumours.

Carcinomas of the cervix may be categorized on morphological grounds into four main groups: squamous carcinomas; adenocarcinomas; neuro-endocrine tumours; and others including adenosquamous carcinomas. Each group contains several morphological subvariants. Invasive squamous carcinomas and adenocarcinomas are preceded by cervical intra-epithelial neoplasia and cervical glandular intra-epithelial neoplasia, respectively. Each is graded into low and high grade. Micro-invasive carcinomas with stromal invasion less than 3mm in depth have a minimal chance of lymph node metastasis. When there is lymph node involvement, the obturator node may be the most common. Presence or absence of lymph node involvement, tumour size and depth of invasion are the important independent histopathological indicators of prognosis. The presence or absence of vascular space invasion is a valuable prognostic indicator. Small cell carcinomas, large cell neuro-endocrine carcinomas and possibly adenoid cystic carcinomas are aggressive. With these exceptions, it is doubtful whether tumour type is of much clinical significance. Tumour grade, as currently assessed, is of no significant value.

Adenocarcinoma↗
PubMed2002

Detection of human papillomavirus in large cell neuroendocrine carcinoma of the uterine cervix: a study of 12 cases.

AIM: To investigate the role of human papillomavirus (HPV) in large cell neuroendocrine carcinoma (LCNEC) of the uterine cervix. METHODS: Twelve archival, immunohistochemically and/or electron microscopically confirmed cases of cervical LCNEC were studied. Non-isotopic in situ hybridisation (NISH) was performed on the formalin fixed, paraffin wax embedded biopsies using digoxigenin labelled probes to HPV types 6, 11, 16, 18, 31, and 33. The tumours were then subjected to polymerase chain reaction (PCR) analysis using GP5+/GP6+ consensus primers to the HPV L1 gene, in addition to type specific primers to the E6 and E6/E7 genes. RESULTS: HPV-16 was detected by NISH and/or PCR in seven of the 12 carcinomas. Two additional tumours were HPV-18 positive by NISH and/or PCR. HPV DNA was not detected in the three remaining cases. CONCLUSION: Integration of high risk HPV, in particular type 16 and to a lesser extent type 18, is associated with this uncommon variant of cervical carcinoma.

Adult↗
PubMed2001

Female adnexal tumours of probable Wolffian origin: an immunohistochemical study comparing tumours, mesonephric remnants and paramesonephric derivatives.

AIMS: To establish an immunohistochemical profile of presumed female adnexal mesonephric tumours (FATWO) for diagnostic purposes and to compare the findings with those of mesonephric and paramesonephric derivatives in order to establish supportive evidence for a mesonephric origin. METHODS AND RESULTS: Standard immunohistochemistry was performed on formalin-fixed tissues. Tumours, mesonephric remnants and paramesonephric structures generally show positive staining for vimentin, CAM 5.2 and cytokeratins 7 and 19 but are negative for CK20 and 34 beta E12. EMA is positive in both mesonephric and paramesonephric derivatives but is negative in the tumours. Glutathione S-transferase mu (GST mu) is generally positive in both tumours and mesonephric derivatives but negative in paramesonephric structures. CONCLUSIONS: Immunohistochemistry plays little part in the diagnosis of FATWO. The tumours are generally cytokeratin and vimentin-positive and EMA-negative. GST mu, as a marker for the mesonephric duct, is a useful adjunct. Our findings of the study support but do not prove that FATWOs are of mesonephric origin.

Adnexal Diseases↗
PubMed2001

Monoclonal antibody SM047 as an immunohistochemical marker of ovarian adenocarcinoma.

AIMS: This study describes the generation of a monoclonal antibody designated SM047 which binds to an epitope that is displayed by a multivalent antigen associated with the glycocalyx of ovarian adenocarcinoma cells. The study also investigates SM047 staining in adenocarcinomas of diverse sites in order to determine whether the antibody is specific for ovarian adenocarcinoma and of value in the confirmation of an ovarian origin when the site of primary tumour is unknown. METHODS AND RESULTS: SM047, an IgM monoclonal antibody, was the product of hybridoma cells derived from fusion of SP2 myeloma cells with splenocytes of a mouse that had been immunized with a membrane preparation of tumour (ovarian serous cystadenocarcinoma) and boosted with cells from a cell line established from a similar tumour in a different patient. Sixty-two primary ovarian adenocarcinomas (28 serous, 23 mucinous, five endometrioid and six clear cell), 69 adenocarcinomas arising primary at other sites and 10 mesotheliomas were stained with SM047. There was positive membrane staining, which was usually strong and widespread, in 27 of 28 ovarian serous carcinomas and in all ovarian endometrioid and clear cell carcinomas. Most ovarian mucinous tumours were negative or exhibited weak cytoplasmic staining. Staining was variable in the other tumours but there was positive staining of most endometrial, endocervical and pancreatic adenocarcinomas. Most colonic adenocarcinomas were negative or exhibited weak cytoplasmic staining. CONCLUSIONS: SM047 is strongly expressed in most ovarian serous adenocarcinomas and in other female genital tract adenocarcinomas, with the exception of ovarian mucinous tumours. The antibody may be useful in confirming the ovarian origin of an adenocarcinoma when used as part of a larger panel. This is especially so in the distinction between a non-mucinous ovarian adenocarcinoma, which usually exhibits strong membranous staining, and a colonic adenocarcinoma which is usually negative or exhibits weak cytoplasmic staining. These findings need to be confirmed by further study of larger numbers of cases.

Adenocarcinoma↗
PubMed2001

Distribution of alpha glutathione S-transferase in ovarian neoplasms: an immunohistochemical study.

AIMS: Alpha glutathione S-transferase (alpha-GST) has been shown to be an immunohistochemical marker for delta(4-5) isomerase, an enzyme active in steroidogenesis. The purpose of this study was to document the distribution of alpha-GST in ovarian neoplasms in order to evaluate its usefulness as a diagnostic tool. METHODS AND RESULTS: A total of 92 tumours (25 sex cord/stromal, 53 epithelial and 14 germ cell) were subjected to immunohistochemistry using a commercially available polyclonal antibody to alpha-GST. The avidin-biotin complex was used as a detection system. Positive staining was found in luteinized stromal cells of all tumour types (58/92). This included the Leydig cells of Sertoli-Leydig cell tumours (7/7) and was particularly prominent in the stromal cells of both benign and malignant mucinous tumours (24/25). Granulosa and Sertoli cells showed weak or no intracytoplasmic staining, which is expected because they do not normally produce androstenedione. They did show some intranuclear staining. Malignant mucinous (12/25) and occasional other epithelial tumours showed focal intracytoplasmic positive staining. Yolk sac tumours showed focal positivity (7/8). CONCLUSIONS: Intracytoplasmic staining of stromal cells is considered to indicate steroidogenesis and intranuclear staining the intracytoplasmic transport function of alpha-GST. The intracytoplasmic staining of mucinous carcinomas might represent an up-regulation of some detoxification function. The findings suggest that antibody to alpha-GST has some value in the investigation of ovarian pathology and could readily be included in any panel of antibodies used to investigate ovarian neoplasms of uncertain histogenesis.

Female↗
PubMed1999

Sclerosing stromal tumors, thecomas, and fibromas of the ovary: an immunohistochemical profile.

The immunohistochemistry of 11 sclerosing stromal tumors (SSTs), 11 fibromas, and 5 thecomas was studied to determine criteria for the assessment of 5 densely sclerotic, calcified ovarian tumors of uncertain diagnosis occurring in young women. The results indicate that the staining pattern for alpha glutathione S-transferase can be used to distinguish SSTs, fibromas, and thecomas. CD34, by highlighting the vascular pattern and density, can be used to distinguish between SSTs and other tumors in the thecoma-fibroma group. Alpha-inhibin and calretinin mirrored the alpha glutathione S-transferase staining. Vimentin, smooth muscle actin, and muscle specific actin were generally positive, but desmin was negative in all but one tumor. These results suggest that at least four of the five tumors of uncertain diagnosis were SSTs that had undergone end-stage sclerosis and calcification.

Actins↗
PubMed1999

Distribution of glutathione S-transferases in the human ovary: an immunohistochemical study.

The glutathione S-transferases (GSTs) are a family of isoenzymes with several functions. These include the metabolism of endogenous and exogenous toxic compounds, an isomerase activity in steroidogenesis and intracellular transport. This study has used immunohistochemistry to demonstrate the distribution of the three classes of GST (alpha, mu and pi) in the human ovary at different stages of the menstrual cycle. Alpha-GST was found in cells related to steroid hormone production and probably acts as a delta4-5 isomerase. Mu-GST was predominantly found in the non-luteinized stromal cells and its function is obscure. Pi-GST was found in surface 'epithelial' inclusions and the media of arteries where it is thought to play a detoxifying role.

Adult↗
PubMed1998

Immunocytochemical localization of adenylyl cyclase in human myometrium.

The enzyme adenylyl cyclase (AC) plays a pivotal role in smooth muscle relaxation. Biochemical evidence suggests that AC is predominantly located in the outer layers of the myometrium; however, neither immunocytochemical nor histochemical studies have been undertaken to demonstrate the specific cellular distribution of the enzyme in this tissue. As part of an ongoing study of the human myometrium, a polyclonal antibody against types V and VI AC was used to detect the presence of these isoforms in sections of formalin-fixed, wax-embedded myometrial tissue. A positive reaction was seen in the cytoplasm of the smooth muscle cells with the midmyometrial area having the greatest number of positive cells, when compared to the subserosal and subendometrial areas. It is hypothesized that AC isoform type VI is the predominant isoform present in the myometrium and that the percentage distribution of positive cells reflects the area of highest myometrial activity during parturition.

Adenylyl Cyclases↗
PubMed1998

Xanthomatous leiomyosarcoma of the uterine cervix.

A 52-year-old woman underwent a hysterectomy for a large tumor of the uterine cervix that was shown to be a xanthomatous leiomyosarcoma (LMS) by histologic examination, the first example of this tumor in this site. Two previous similar tumors have been reported in the uterine corpus.

Biomarkers, Tumor↗
PubMed1998

Leiomyomas of the uterine cervix: a study of frequency.

Leiomyomas of the cervix are said to be uncommon. To establish their frequency, 661 consecutive total hysterectomy specimens were examined macroscopically and microscopically. Myometrial leiomyomas were present in 427 uteri (64.6%) but cervical leiomyoma were present in only 4 (0.6%). One of these was 6 mm in diameter and occurred in a uterus without fibroids elsewhere. Only two could have been considered clinically significant. An additional six cases showed submucous fibroids of the body of the uterus protruding as a polyp into the endocervical canal but these were not considered cervical leiomyomas. The conclusion of the study is that cervical leiomyomas are extremely uncommon.

Adolescent↗
PubMed1998

The significance of smooth muscle bundles in the endocervical submucosa.

In approximately 25% of uterine cervices there are bundles of smooth muscle in the immediate submucosa of the endocervix usually in the region of the transformation zone. They are morphologically and immunohistochemically different from the inherent muscle deeper in the cervix in that they have more cytoplasm, are arranged in bundles not separated by collagen, and do not contain oestrogen or progesterone receptors. They are more commonly found during the reproductive years becoming less common after the menopause, but there is no association with parity, the use of exogenous steroids, uterine fibromyomas or uterine prolapse. At present it can only be concluded that their presence represents a morphological variation.

Age Distribution↗
PubMed1997

Smooth muscle neoplasms of the uterus.

Recent investigations, using DNA technology, of the molecular biology of smooth muscle tumours of the uterus have confirmed their monoclonality and have strengthened the view that oestrogen and oestrogen receptors play a major role in the pathogenesis of fibromyomata. In addition, increasing evidence suggests that progesterone, insulin-like growth factors, epidermal growth factors and other proteins are also involved. The mechanisms whereby gonadotrophin-releasing hormone agonists cause shrinkage of fibromyomata remain controversial but both vascular changes and cellular atrophy appear to play a role. A shift of emphasis in the study of fibromyomata has resulted from the demonstration that the myometrium adjacent to fibromyomata is not normal and shows some similarities to the tumours themselves.

Cytogenetics↗
PubMed1996

Anatomical variation of the oestrogen receptor in the non-neoplastic myometrium of fibromyomatous uteri.

Myometrial tissues from a total of 30 normal and 30 fibromyomatous uteri were compared in order to assess whether the oestrogen receptor distribution is similar for both types. All patients concerned were premenopausal with no history of exogenous hormone usage. Material taken from the subserosal, midmyometrial and subendometrial regions of both the fundus and the lower segment was stained by immunocytochemistry for the oestrogen receptor. No significant difference in the oestrogen receptor content was noted between the fundus and the lower segment in either the normal or the fibromyomatous myometria. Similarly, the phase of the menstrual cycle did not affect the total receptor content of either group of tissue. The oestrogen receptor content in the non-neoplastic portion of the fibromyomatous myometria was highest in the subendometrial and lowest in the subserosal region. The differences in receptor content between normal and fibromyomatous myometria were minimal in the subendometrial region but marked in the subserosal region. The myometrium of fibromyomatous uteri thus expresses significantly increased levels of oestrogen receptor, and the pathogenesis of fibromyomata may be related to an inherent abnormality in the myometrium.

Adult↗
PubMed1996

Postpartum microneuromas of the uterine cervix.

The cervices of 300 hysterectomy specimens have been examined for the presence of abnormal nerves morphologically resembling traumatic neuromas. These were present in 165 uteri (55%) overall but in only two of the 48 nulliparous patients (4%), indicating a probable causation by parturition. The microneuromas could be graded. The larger, more complex lesions were associated with more extensive involvement of the cervix but not with increased parity.

Cervix Uteri↗
PubMed1995

Anatomical variation of the oestrogen receptor in normal myometrium.

Tissue from 20 surgically resected uteri was examined in order to test the hypothesis that the oestrogen receptor content of the myometrium may not be uniform throughout the uterus. All patients were premenopausal, had no history of any exogenous steroid hormone use and were in the proliferative phase of the menstrual cycle. Material was taken from the subserosal, midmyometrical and subendometrial regions of both the fundal and lower uterine segments. Care was taken to remove all endometrium. Suitable samples were analysed by radioimmunoassay (RIA) for oestrogen receptors. An adjacent block from each area was fixed in formalin and stained immunocytochemically for oestrogen receptors. The results of the RIA show a significantly higher receptor content in the subendometrial region than in either the midmyometrial or the subserosal region. No significant difference was demonstrated between the numbers of receptors in the fundus and in the lower uterine segments. The differences were also well demonstrated by immunocytochemistry, according to which 83% of all cells counted in the subendometrial region were positive, while only 61% of cells in the middle and 47% of those in the subserosal region were positive.

Adult↗
PubMed1992

Mucin production in cervical intra-epithelial neoplasia.

Fifty sections showing cervical intra-epithelial neoplasia grade III were stained with mucicarmine and periodic acid-Schiff reagents to demonstrate mucin production. Seven of these showed mucin within the neoplastic cells (14%); these cases were considered to be a form of adenosquamous carcinoma in situ and lend support to the hypothesis that invasive adenosquamous carcinomas arise from an indifferent reserve cell.

Adenocarcinoma↗
PubMed1992

Placental bed biopsies in placental abruption.

OBJECTIVE: To investigate structural changes in the uteroplacental blood vessels in association with placental abruption. DESIGN: Prospective descriptive study. SUBJECTS: 18 women with clinical evidence of severe placental abruption delivered by caesarean section. INTERVENTIONS: Placental bed biopsies were obtained at caesarean section and studied histologically. RESULTS: Six specimens did not include trophoblast in the myometrium and were therefore not representative of the placental bed. Of the 12 representative specimens, seven demonstrated absence of physiological transformation of the utero-placental arteries (four of these were from hypertensive patients). Four biopsies showed abnormal vascular structures deep in the myometrium. One of these abnormal vessels included a fresh plug and extensive surrounding intramyometrial haemorrhage. CONCLUSIONS: Vascular malformations in association with placental abruption may be the result of trophoblastic invasion and could be the site of vessel rupture. Further descriptive and comparative studies are needed.

Abruptio Placentae↗