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Biomedical subjects

C H Buckley

Publications and source records attributed to C H Buckley.

At least 55 records · Page 3Linked to original sources

Subinvolution of the uteroplacental arteries: an immunohistochemical study.

Subinvolution of uteroplacental arteries is a well-recognized cause of hemorrhage in the postpartum period. Although the physiological changes in these arteries during pregnancy are well documented, the sequence of events in normal involution is largely unknown. A recent immunohistochemical study has raised the possibility of an abnormal interaction between maternal uterine cells and fetal trophoblast in subinvolution. An indirect immunoperoxidase technique was used to compare deposition of complement components and immunoglobulin in subinvoluted and normally involuted uteroplacental arteries in 25 cases of postpartum hemorrhage. Deposits of C1q, C3d, C4, and C9 were detected within the walls of normally involuted vessels, whereas deposition of C1q, C3d, and C4 was absent in subinvoluted vessels; C9 was detected only focally. Deposition of immunoglobulins G, A, and M mirrored those described for complement components. The results suggest that immunological factors are necessary for the process of normal involution of uteroplacental arteries and are deficient in subinvoluted vessels.

Arteries↗

Patterns of immunohistochemical staining for proliferating cell nuclear antigen and p53 in benign and neoplastic human endometrium.

Immunohistochemical staining was carried out on a spectrum of normal, hyperplastic and malignant endometrial curettings, for proliferating cell nuclear antigen--PCNA (using the monoclonal antibody PC10) and for abnormally stabilized p53 (using the polyclonal antibody CM-1). The mean proportion of glandular epithelial cells showing PCNA immunoreactivity was significantly lower in atypical hyperplasia/intra-endometrial adenocarcinoma than in invasive adenocarcinoma, but the degree of overlap between the cases was such that this was not considered to be of diagnostic value. p53 immunoreactivity was detected in 47% of invasive adenocarcinomas and in a much smaller proportion of endometria showing simple hyperplasia and atypical hyperplasia, but staining was only focal in the last two conditions. The majority of p53-positive invasive adenocarcinomas had a large proportion of glandular epithelial cells expressing PCNA, but a significant number of p53-negative cases also had a high PC10 index. This suggests that, in endometrial neoplasia, there is not a simple relationship between abnormally stabilized p53 and PCNA expression.

Adenocarcinoma↗

The Royal College of Obstetricians and Gynaecologists micro-invasive carcinoma of the cervix study: preliminary results.

OBJECTIVES: To determine how micro-invasive carcinoma of the cervix is diagnosed and treated in the United Kingdom. To record the frequency of the various pathological features which comprise the histological diagnosis of micro-invasion, and to assess their relevance to outcome. DESIGN: Prospective observational study. SETTING: Hospitals throughout the United Kingdom. SUBJECTS: Two hundred and eighty-six cases were submitted for entry into the study. Following independent review of the histological material 116 cases were excluded: 41 were not accompanied by histological slides for review, 55 had no evidence of invasive disease, 17 had invasive disease greater than FIGO Stage 1a, and three were adenocarcinomas. The remaining 170 cases were registered for the study but follow up was incomplete in 18. This report concerns the 152 women with complete follow up to 1991. RESULTS: The age of the 152 women ranged from 22 to 65 years (median 36 years). In 116 women (76%) the diagnosis was made by cone biopsy (cold knife, loop diathermy, or laser) or wedge biopsy, in 9 women (6%) the diagnosis was made by hysterectomy, and in 27 women (18%) punch biopsy suggested an invasive lesion and subsequent excisional treatment (including radical hysterectomy with node dissection in three) demonstrated micro-invasion. The depth of invasion was up to 3 mm in 142 women (93%) and 3.1 to 5 mm in 10 women (7%). Capillary-like space involvement was present in 12 women (8%). Treatment methods used were local cervical surgery in 79 women (52%), simple hysterectomy in 63 (41%), and radical hysterectomy in 10 (7%). There was only one known recurrence and death due to cervical carcinoma. CONCLUSION: There is no uniformity in the management of micro-invasive carcinoma of the cervix. The frequency of recurrence, lymph metastases, and death is low. Nonradical surgery appears to give satisfactory results.

Adult↗

Use of proliferation cell nuclear antigen immunoreactivity for distinguishing hydropic abortions from partial hydatidiform moles.

AIMS: To determine whether the expression of proliferating cell nuclear antigen (PCNA) in villous cytotrophoblast could distinguish between placental tissue from a hydropic abortion and that from a partial hydatidiform mole. METHODS: Tissue from 18 partial hydatidiform moles, 15 hydropic abortions, five normal first trimester placentas and five normal full term placentas were immunostained for expression of PCNA, using the monoclonal antibody PC10. RESULTS: PCNA immunoreactivity was very much higher in the cytotrophoblast of normal first trimester placentas than in normal term placentas. Villous tissue from partial hydatidiform moles showed, on average, less immunoreactivity for PCNA than did villous tissue from hydropic abortions. CONCLUSIONS: Immunostaining for PCNA is of no value for differentiating between partial hydatidiform moles and hydropic abortions. The findings indicate that trophoblastic proliferation or hyperplasia is not a feature of partial hydatidiform moles.

Abortion, Spontaneous↗

Prognostic value of epidermal growth factor receptor expression in cervical carcinoma.

AIMS: To investigate the pattern of epidermal growth factor receptor expression and its prognostic value in the three main types of cervical carcinoma. METHODS: 62 cases of stage IB/IIA cervical carcinoma, all with a minimum of five years of follow up, were studied. Representative sections were stained for mucin to permit accurate tumour typing and a standard avidin-biotin immunoperoxidase technique using the polyclonal antibody 12E was used to demonstrate the presence of epidermal growth factor receptor. RESULTS: A proportion of all three tumour types expressed epidermal growth factor receptor, it being most common in squamous cell carcinomas (50%). Overall, there was a correlation between epidermal growth factor expression and mortality. This was particularly obvious in the absence of lymph node metastases. When the individual tumour types were considered this association with prognosis was not demonstrable for squamous cell carcinomas or adenocarcinomas but was a very prominent feature of adenosquamous carcinomas. CONCLUSIONS: Immunohistochemical demonstration of epidermal growth factor receptor expression may be useful in identifying those patients with a poor prognosis, particularly those with adenosquamous carcinomas which have not metastasised to the regional lymph nodes.

Adenocarcinoma↗

Cytoskeletal filaments in the smooth muscle cells of uterine leiomyomata and myometrium: an ultrastructural and immunohistochemical analysis.

The filamentous components of the cytoskeleton in smooth muscle cells of leiomyomata and normal myometrium were studied by immunohistochemistry and electron microscopy. Fourteen patients hysterectomised for non-malignant disease provided leiomyomata of conventional histological type and histologically normal myometrium: four samples of fetal myometrium were studied by immunohistochemistry alone. All samples of leiomyoma and myometrium were strongly positive for alpha-smooth muscle actin and desmin, the latter often as paranuclear columns or granules. Vimentin was also stained in most samples but less intensely, while cytokeratin stained in about half the samples with an intensity comparable to that of vimentin. By electron microscopy, myofilaments with focal densities were abundant in both normal myometrium and leiomyomata. Intermediate filaments corresponding to the desmin and vimentin demonstrated by immunohistochemistry were also recognised in a variety of architectural arrangements. At one extreme, comparatively small numbers of filaments were loosely distributed around membranous organelles; at the other, filaments formed conspicuous aggregates, largely excluding other organelles and corresponding to the paranuclear granules seen by immunohistochemistry. A comparison of these findings with those of the literature and comments on the possible significance and origin of these aggregates are provided.

Cytoskeleton↗

Carcinoma of the cervix: an analysis of prognostic factors, treatment and patterns of failure following Wertheims hysterectomy.

A clinicopathologic analysis of 70 patients treated by radiotherapy and/or chemotherapy following primary radical surgery has been undertaken. Clinical stage at presentation was IB (58 patients) and IIA (12 patients). Thirty-five patients (50%) had squamous carcinoma, 23 (33%) had adenosquamous carcinoma, 9 (13%) had adenocarcinoma and 3 (4%) had an undifferentiated neoplasm. The reasons for further treatment were: (i) pelvic lymph node metastases (PLNM), 35 (50%); (ii) inadequate central clearance (ICC), 13 (18%); (iii) recurrent disease (RD), 17 (24%); (iv) others, 5 (8%) cases. Sixty-seven patients had radiotherapy, one of whom also received adjuvant chemotherapy, three patients had chemotherapy alone, and 12 patients received chemotherapy for recurrence following radiotherapy. The 5-year survival in the above referral groups were: (i) 66%; (ii) 62%; (iii) 12%. The site of relapse following treatment was primarily pelvic in groups 2 (ICC) and 3 (RD) and extrapelvic in group 1 (PLNM). Of the histologic parameters studied the only factor of statistical significance in predicting outcome in this group who are recognized to have a generally poor prognosis was the presence of parametrial extension (P = 0.0066). Six cases (9%) developed complications following therapy, lymphoedema being the most common (66%).

Journal Article↗

Endometrium in in-vitro fertilization cycles: morphological and functional differentiation in the implantation phase.

Secretory differentiation of endometrium after multiple follicular stimulation using gonadotrophin releasing hormone and human menopausal gonadotrophin has been studied both histologically and immunohistochemically in 30 women undergoing in-vitro fertilization treatment. None had embryo transfer. Patients were randomly allocated to receive luteal phase support with a single dose of human chorionic gonadotrophin. The latter failed to produce any significant enhancement of endometrial structure or secretions. Appropriate glandular morphology was present in a greater proportion of those who were successfully stimulated than those who responded poorly. However, defective secretion of the cycle-dependent component studied, using monoclonal antibody D9B1, was demonstrated in two-thirds of cases regardless of the ovarian response. Early vascular maturation in the stroma was a common finding, and was thus considered as a feature of structural modulation of these endometria.

Antibodies, Monoclonal↗

Expression of an oestrogen receptor-related antigen in human endometrium: a microphotometric study.

The expression of an oestrogen receptor-related antigen has been measured by microspectrophotometry in the glandular epithelium and stroma of tissue sections from endometrial biopsies of women administered exogenous replacement of sex steroids because of premature ovarian failure. We have demonstrated that previously dormant endometrium is capable of expressing an antigen related to oestrogen receptors and that its distribution is influenced by the sex steroid environment. Immunohistochemical staining was more intense (P less than 0.001) in the glandular compared to the stromal cells in tissue exposed solely to oestradiol. With the administration of progesterone, the stromal staining intensity increased (P less than 0.0001) and that of the glandular staining decreased (P less than 0.0001). No assumption, however, has been made to infer that colour is stoichiometrically related to the concentration of antigen present. Further validation of immunohistochemical procedures is required because histological localization and measurement of immunohistochemical staining may be straightforward, but its relationship to antigen concentration remains unproven.

Antibodies, Monoclonal↗

The distribution of type IV collagen in invasive carcinoma of the uterine cervix.

The presence of type IV collagen at the tumour/stromal interface of invasive carcinoma of the cervix was evaluated in 60 cases. It was assessed semi-quantitatively according to its staining characteristics, and expressed as: thick, with or without minimal discontinuity; thin, with or without moderate discontinuity; fragmentary or absent. In each case the tumour type was identified, the differentiation, growth pattern and peritumoural inflammatory infiltrate was graded and lymph node status established. There was, overall, a significant correlation between a paucity of type IV collagen and a poorer prognosis and an infiltrating growth pattern. There was a highly significant correlation for adenocarcinomas in relation to poor outcome, infiltrating growth pattern and lymph node metastases. By contrast, no statistically significant correlation was found between paucity of type IV collagen and the other parameters for either squamous or adenosquamous carcinomas. The presence of absence of type IV collagen may be a useful prognostic marker, particularly for adenocarcinomas, and may play a part in the invasive and metastatic process.

Adenocarcinoma↗

A prospective study of conization of the cervix in the management of cervical intraepithelial glandular neoplasia (CIGN)--a preliminary report.

OBJECTIVE: To assess the efficacy of cervical conization as primary management of cervical intraepithelial glandular neoplasia (CIGN). DESIGN: A multicentre prospective cohort study. SETTING: CRC Clinical Trials Unit, Birmingham. SUBJECTS: 84 women registered with the Unit between May 1986 and January 1989. After excluding 33 women, 51 who had been managed in accordance with the described protocol and had the presence of CIGN confirmed by central review of diagnostic histopathological material were included in the study. INTERVENTION/PROTOCOL: Women with CIGN diagnosed on a cervical cone specimen were managed in accordance with a specific protocol: (a) women with negative cone margins were managed conservatively and followed up with regular cervical cytological and colposcopic examinations; (b) women with involved cone margins were managed by hysterectomy. MAIN OUTCOME MEASURES: Presence or absence of CIGN at cone margins, results of cervical cytological examinations following conization, results of histopathological assessment of any surgical specimens taken after initial cone biopsy. RESULTS: Of the 51 women with confirmed CIGN, managed by conization, 14 (27%) were aged 30 or less and 15 (29%) were nulliparous. Thirty five women who had a cone biopsy showing margins free of CIGN have been managed by conization alone. After a median follow-up period of 12 months there is no apparent residual CIGN or invasive disease in this group. Thirteen women have had further surgical procedures (according to protocol) and two have had a hysterectomy for benign gynaecological disorders. Eight further procedures were carried out because the original cone biopsy had margins involved with CIGN, and only one of them was found to have residual CIGN. The other five procedures were carried out solely because of abnormal cytology, only one of them had a diagnosis of CIN 1. A total of 10 women had cytological abnormality following cone biopsy, one had CIGN, one had CIN 1 and a third had CIN 3. CONCLUSIONS: Our preliminary data suggests that when a diagnosis of CIGN is made upon a cone biopsy, further surgery is unnecessary in those women in whom the margins of the cone specimen are free of disease. Cytological and colposcopic follow up, including cytological sampling of the endocervical canal, is recommended for these women.

Adult↗

Prognostic value of c-erbB-2 expression in uterine cervical carcinoma.

AIMS: To study the pattern of expression and prognostic importance of c-erbB-2 protein in cervical carcinoma. METHODS: Sixty two cases of stage IB/IIA cervical carcinoma, representing the three main tumour types, were investigated immunohistochemically for the presence of c-erbB-2 protein expression, using a monoclonal antibody (CB11) to its internal domain. Follow up of at least five years' duration was available in all cases. RESULTS: Definite membrane staining was seen in 38.7% of cases. There was a strong correlation with poor survival (p less than 0.0001) particularly. For those with adenocarcinomas, this was the case when nodal metastases were present. In contrast, for squamous carcinomas and adenosquamous carcinomas, the association with a poor prognosis was most apparent in those patients without lymph node metastases. CONCLUSIONS: These findings raise the possibility that immunostaining for c-erbB-2 protein could be used as a prognostic marker and may help identify those patients for whom early adjuvant treatment might be beneficial.

Adenocarcinoma↗

Germ cell expression of placental alkaline phosphatase in male pseudohermaphroditism.

We have reviewed testes removed from 14 individuals with male pseudohermaphroditism (13 with androgen insensitivity and one with 17 alpha-hydroxylase deficiency) and have studied staining for placental alkaline phosphatase in germ cells. Placental alkaline phosphatase positivity was identified in fetal and premature neonatal controls but not in cryptorchid males or normal autopsy control material from boys older than 6 months. It was present in autopsy testes younger than 6 months and cases of androgen insensitivity in boys younger than 8 months, suggesting immaturity. It was also expressed in two patients with male pseudohermaphroditism aged 5 years and 14 years, both of whom had intra-tubular germ cell neoplasia by morphological criteria. Our study confirms the use of placental alkaline phosphatase as a marker of germ cell neoplasia in this specific group who are at high risk of malignancy.

Adolescent↗