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Biomedical subjects

N E Langlois

Publications and source records attributed to N E Langlois.

At least 19 recordsLinked to original sources

Apoptosis and prognosis in cancer: rationale and relevance.

Apoptosis is the biological process by which cells in tissues undergo programmed death. This process is morphologically identifiable and characterised by light and electron microscopy. However, the biological mechanisms underlying this process, as yet, are poorly understood and in need of elucidation. As apoptotic tumour cells can be identified and counted by light microscopy, there has been interest in the application of the enumeration of apoptosis in malignant growths as a putative prognostic marker. This review outlines the rationale for and discusses the relevance of using such an approach in clinical practice.

Animals↗

Angiosarcoma of the penis.

Sarcoma of the penis is rare. We report an angiosarcoma that was essentially an incidental finding, despite the presence of metastatic lesions, in a 46-year-old man who presented with hematemesis and melena. The diagnosis of the primary lesion was confirmed by histology, and the presence of secondary lesions by fine needle aspiration cytology. The patient was given one dose of chemotherapy, but died of a myocardial infarction before being able to receive further treatment. The literature pertaining to this very unusual lesion is discussed.

Hemangiosarcoma↗

Application of the principle of marginal analysis to sampling practice using prostatic chippings as a model.

AIMS: To demonstrate an application of health economic principles in histopathology by using the sampling of transurethral resections of prostate specimens. By demonstrating how marginal costs are calculated the aim is to illustrate that the potential opportunity cost of sampling entire specimens is much greater than would be anticipated by taking average cost, or the cost of producing a histological section alone. METHOD: A mathematical model is used with data obtained from the Aberdeen pathology department files and published estimates of the likely percentage of cancerous chippings in each specimen. RESULTS: The average cost of each cancer detected remains low, between 47 Pounds and 151 Pounds, in all the scenarios examined. However, the marginal costs can become high, exceeding 10,000 Pounds in larger specimens, if all the chippings are processed. CONCLUSIONS: This study demonstrates that there are potential opportunity cost penalties to histopathological services associated with sampling strategies. Although the results are derived from a hypothetical mathematical model using local data that applies only to histopathology, the method could be widely applied. The principles of marginal analysis should be performed by multidisciplinary teams and include outcomes as well as a broader range of costs, including those that arise subsequent to diagnosis.

Costs and Cost Analysis↗

Apoptosis in colorectal carcinoma occurring in patients aged 45 years and under: relationship to prognosis, mitosis, and immunohistochemical demonstration of p53, c-myc and bcl-2 protein products.

The aim of this study was to ascertain whether apoptotic counts have prognostic significance in colorectal cancer and if such counts are related to the expression of proteins implicated in cell cycle regulation. Material from a cohort of patients aged 45 years or less with colorectal carcinoma was re-examined to determine apoptotic and mitotic counts by light microscopy, in addition to assessing p53, c-myc, and bcl-2 protein status by immunohistochemistry. The apoptotic index in the 74 patients who were alive or who had died of colorectal carcinoma ranged from 1.2 per cent to 12.3 per cent and exhibited independent prognostic significance, with high counts predicting better survival (P = 0.02). Mitotic counts were not related to survival, despite a close correlation with apoptosis (r = 0.85). Tumours regarded as not staining with the CM1 antibody for p53 protein demonstrated higher apoptotic counts, compared with those that stained (medians 5.2 and 4.0 per cent, respectively; P = 0.03), but p53 expression was found not to be related to survival. The 68 tumours which stained for c-myc appeared to exhibit higher mitotic counts than those that did not. bcl-2 was detected in only four tumours. The latter two proteins exhibited no apparent relationship to the apoptotic index or survival. Although these results indicate a potential role for apoptotic counting in prognostic prediction in colorectal tumours, this is an uncommon group of patients who exhibited some atypical features. The likelihood of a proportion of cases arising within hereditary non-polyposis colorectal cancer syndrome may limit the application of the findings to a more general population with cancer of the colon and rectum. Further work is required, including critical measurement of reproducibility and assessment of the relative impact of this parameter compared with 'traditional' prognostic markers.

Adolescent↗

Pancreatic tissue in a lateral cervical cyst attached to the thyroid gland--a presumed foregut remnant.

AIM: To report the previously undescribed occurrence of a lateral neck cyst, attached to the thyroid gland, containing pancreatic tissue. METHODS AND RESULTS: A 41-year-old man presented with a recurrent cystic lesion of the thyroid. At thyroidectomy cystic masses containing mucinous material were present in the neck, and there was a nodular lesion attached to the lower pole of the thyroid. Histological examination of the latter lesion revealed an epithelial lined cyst, with pancreatic tissue (exocrine and endocrine) in addition to fat, fibrous tissue, muscle and cartilage in the wall. CONCLUSIONS: The possible origin of this structure is discussed, with the conclusion being that it most likely represents a foregut remnant.

Adult↗

Apoptosis in atypical fibroxanthoma and pleomorphic malignant fibrous histiocytoma.

Explanations for the disparate behavior of atypical fibroxanthoma (AFX) as compared with pleomorphic malignant fibrous histiocytoma (MFH) have included the proposition that the former is a pseudosarcoma. Nonetheless, these tumors are now widely regarded as the same process, but with AFX behaving benignly by virtue of its superficial location. However, a neoplasm's metastastatic potential has been proposed to be related to apoptosis. Therefore, the aim of the present study was to examine apoptotic counts, in conjunction with two important regulators of apoptosis: p53 and bcl-2, to determine if a distinction exists that may account for the different outcomes of these lesions. There was no significant statistical difference between eight AFX and nine pleomorphic MFH in terms of apoptotic behavior, proliferative indexes, p53 protein expression, or presence of bcl-2 product. Therefore, our results further support the contention that AFX should be regarded as a form of pleomorphic MFH, which demonstrates low malignant potential by virtue of its location in readily accessible sites.

Adult↗

A study of the value and prognostic significance of mucin staining in squamous cell carcinoma of the uterine cervix.

One hundred and eighty-one cases of squamous carcinoma of the uterine cervix, which had been retrieved from the archives of Aberdeen Royal Hospital, from 1974 to 1988, were stained with periodic acid-Schiff following diastase and alcian blue to ascertain the value and prognostic significance of demonstrating the presence of mucin. Each case was typed and graded on a representative haematoxylin and eosin section, while the age at diagnosis, stage and survival (within a minimum five year follow-up) was obtained from examination of hospital case notes and death certificates. The data was analysed by Cox regression which revealed that the demonstration of mucin, either by both stains or only one method, had no bearing on prognosis. On this basis, it is concluded that routine mucin staining of squamous carcinomas of the uterine cervix is not justified.

Biomarkers, Tumor↗

An evaluation of the staining of lymphomas and normal tissues by the rabbit polyclonal antibody to protein gene product 9.5 following non-enzymatic retrieval of antigen.

We have previously described the staining of normal follicle centre lymphoid cells by the rabbit polyclonal antibody to protein gene product 9.5 (PGP9.5), following an antigen unmasking step employing heat pretreatment. Applying this finding to a range of lymphomas to determine whether this phenomenon could have a role in identifying lymphomas of follicle centre origin revealed no relationship between type or grade of lymphoma and staining of neoplastic cells. Testing a range of normal tissues following antigen retrieval displayed increased sensitivity and a greater range of tissue positivity. Immunoblots of gel electrophoresed tonsil and brain extract were performed. Although subjecting these blots to antigen unmasking increased sensitivity, no novel epitopes, in terms of additional bands, appeared. This suggested that antibody specificity remained unaltered.

Blotting, Western↗

Non-enzymatic retrieval of antigen permits staining of follicle centre cells by the rabbit polyclonal antibody to protein gene product 9.5.

The rabbit polyclonal antibody to protein gene product 9.5 (PGP9.5) will detect the L1 isoenzyme of ubiquitin carboxy-terminal hydrolase (UCH), which is a marker for neurones and neuroendocrine tissue. We re-evaluated this antibody using the technique of non-enzymatic antigen retrieval (boiling sections in citrate buffer, heated by microwave oven) followed by streptavidin-biotin-peroxidase staining. Due to the fortuitous choice of appendix as positive control material containing small nerves, we found strong, repeatable cytoplasmic and nuclear staining of lymphoid follicle centre cells in addition to neural tissue. This effect could be repeated on other lymphoid tissues and was not dependent on microwave heating, but did require boiling in an ionic buffer solution. Staining was also observed with a fresh batch of antibody and with four of the five different batches of antibody which were supplied to us. This pattern was not obtained in fresh tissue, in fixed material following trypsinization, or by increasing the primary antibody concentration. We suggest that the boiling of sections in citrate buffer is exposing an epitope for the anti-PGP9.5 antibody which is inaccessible in the native or fixed state and therefore we would recommend retesting of antibody specificity following non-enzymatic retrieval of antigen.

Animals↗

Mucosal changes in the large bowel with endometriosis: a possible cause of misdiagnosis of colitis?

Endometriotic deposits are not uncommon in the large bowel of women. Because the symptoms produced by endometriosis may lead to investigation by colorectal endoscopic biopsy, the aims of this study were to assess the range of mucosal abnormalities that may occur and to determine whether this could represent a significant potential diagnostic problem. We found mucosal changes in eight of 10 cases of colorectal endometriosis; however, the abnormalities (ulceration, gland architectural disturbance, crypt abscess formation, increased inflammatory cell presence, and smooth muscle fibers between glands in the mucosa) were focal and directly related to endometrial deposits. In one case an abnormal colonic biopsy specimen from a patient with endometriosis supported the erroneous clinical diagnosis of Crohn's disease. Comparing a group of women with endometriosis to a group with adenomyosis of the uterus showed that although more women with endometriosis have endoscopic large bowel biopsies, there was no significant excess of biopsy specimens showing inflammatory changes. Our conclusion is that the endometriosis of the large bowel can masquerade as inflammatory bowel disease or ischemic changes and the possibility should be borne in mind, particularly in cases with atypical clinical features or very focal histological changes.

Adult↗

Plunging ranula: a case report and a literature review.

The plunging ranula is a mucous extravasation cyst of the sublingual gland. It is slightly more common in females, shows no side preference, and is more prevalent in the second and third decades of life. It typically manifests as a painless, nonmobile swelling in the neck and in four of five cases is associated with an intraoral ranula or swelling. If there is no history of an oral ranula the clinical diagnosis is difficult, and it may be left to the reporting pathologist to give the correct diagnosis. The histologic appearance is characteristically of a cyst, devoid of epithelium or endothelium, with a vascular fibro-connective tissue wall containing some chronic inflammatory cells and macrophages stuffed with mucin. The correct diagnosis is essential for the most effective treatment, which is excision of the sublingual gland.

Child↗