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Biomedical subjects

M M Kennedy

Publications and source records attributed to M M Kennedy.

At least 19 recordsLinked to original sources
PubMed2000

Immune cell infiltrates and prognosis in primary carcinoma of the lung.

The prognostic significance of immune cell infiltrates in surgically resected human lung cancer was investigated in 710 patients. Lymphoid infiltrates were quantified on both standard H&E stained sections and, in a subset of 95 cases, using immunohistochemistry and antibodies to CD3, CD8, CD57, CD68, CD79a and S100 to identify various immune cell types. Subjective grading (low, moderate, high) of lymphoid cell infiltrates on H&E sections of tumour and measurement, using image analysis, of overall level of tumour infiltration by any of the immunohistochemically labelled specific immune cell types of the stained sections showed no prognostic significance. However, when a distinction between peritumoural and intratumoural infiltration by particular cell types was made, intratumoural infiltration by high levels of CD3+ and S100+ cells was associated with longer post-operative survival (P = 0.02 and P = 0.045, respectively). In lung cancer, subjective assessment of tumour lymphoid infiltration and overall levels of infiltration by particular immune cell types carries no prognostic significance. Intratumoural infiltration by relatively high numbers of CD3+ T-lymphocytes and Langerhans cells (S100+) is associated with a better patient outcome.

Adult↗
PubMed2000

Small cell malignant melanoma: a variant of naevoid melanoma. Clinicopathological features and histological differential diagnosis.

AIMS: To describe the clinical and histopathological features of a rare variant of naevoid melanoma, small cell melanoma, and discuss the histological differential diagnoses. METHODS: The clinical and histological features of cases of malignant melanoma with the histological features of small (non-Merkel like) melanoma were reviewed and documented. In addition, five cases had available material for immunohistochemistry and this was performed using antibodies to the S100 protein and melan-A, and the HMB-45 antibody. RESULTS: There were 15 cases of small cell melanoma from 14 (10 female, four male) patients, aged between 30 and 77 (mean, 48.6) years. The trunk was the most common location. In more than half the cases, the provisional diagnosis was melanoma/borderline lesion. All shared similar histological appearances of an intraepidermal component of in situ melanoma and a dermal component of nests of cells with hyperchromatic nuclei and scanty cytoplasm, usually in tightly packed nests. All components (junctional and intradermal) of the lesions investigated by immunohistochemistry were positive both for S100 protein and melan-A. All junctional components were positive with HMB-45, but with variable staining of the dermal components with this antibody. CONCLUSIONS: Small cell malignant melanoma is postulated to be a distinct histopathological entity and a rare variant of naevoid melanoma. Such lesions can be difficult to interpret and easily missed at scanning magnification because the cells of the dermal component mimic benign naevus cells.

Adult↗
PubMed1999

Cyclin D1 expression and HHV8 in Kaposi sarcoma.

BACKGROUND: Human herpesvirus 8 (HHV8) appears to be the agent responsible for Kaposi sarcoma. The mechanism remains undetermined but may involve cell cycle regulating genes including D type cyclins which are pivotal in cell cycle progression. Recent HHV8 genetic analysis has revealed the presence of a v-cyclin which is homologous to D type cyclins. AIMS: First, to assess whether there is an independent relation between endogenous cyclin D1 expression in Kaposi sarcoma and HHV8 status; second to determine whether v-cyclin mRNA expression varies with Kaposi sarcoma stage. METHODS: Cyclin D1 immunohistochemistry was performed on 17 paraffin embedded Kaposi sarcoma samples from 16 patients. HHV8 status was assessed in 15 of these using nested polymerase chain reaction (PCR) to ORF 26 and the newly described technique of TaqMan PCR. An additional 10 fresh Kaposi sarcoma samples (early and nodular) were examined for HHV8 v-cyclin RNA. RESULTS: One case, which did not contain amplifiable HHV8, showed strong cyclin D1 staining. The remaining cases were negative or weakly staining; v-cyclin transcript load was higher in early Kaposi sarcoma. CONCLUSIONS: While endogenous cyclin D1 expression is independent of HHV8 status, v-cyclin transcription is higher in early lesions, supporting the "viral hit" hypothesis.

Cyclin D1↗
PubMed1999

CD40 upregulation is independent of HHV-8 in the pathogenesis of Kaposi's sarcoma.

AIMS: Human herpesvirus 8 (HHV-8) is now acknowledged as the infective cofactor in the pathogenesis of Kaposi's sarcoma. The mode by which HHV-8 causes Kaposi's sarcoma is unresolved and it is probable that it acts in conjunction with other factors including cytokines, anti-apoptosis proteins, and cell surface receptors. CD40, a cell membrane receptor belonging to the tumour necrosis factor receptor super family, promotes B cell survival and is expressed constitutively on endothelial cells. It is upregulated on cytokine treatment and has been documented recently in Kaposi's sarcoma. Because the HHV-8 genome contains cytokine homologues, this study investigated whether CD40 expression in Kaposi's sarcoma correlated with HHV-8 status, using a unique set of HHV-8 positive and negative specimens. METHODS: Twenty one paraffin wax embedded samples of Kaposi's sarcoma were selected, of which 18 were screened for the presence of HHV-8 using both conventional solution phase and TaqMan polymerase chain reaction (PCR). CD40 immunohistochemistry was assessed using a biotinylated amplification system. Staining was scored semiquantitatively. RESULTS: The results indicated that the expression of CD40 is independent of viral status, being present in both HHV-8 positive and negative specimens. CONCLUSIONS: This suggests that HHV-8 promotes Kaposi's sarcoma cell survival following infection by mechanisms other than those involving CD40.

Antigens, Neoplasm↗
PubMed1999

Tamoxifen and the endometrium: review of 102 cases and comparison with HRT-related and non-HRT-related endometrial pathology.

Tamoxifen, a synthetic anti-estrogen that paradoxically acts as a partial estrogen agonist on the endometrium, is associated with an increased frequency of proliferative endometrial lesions, including hyperplasias, neoplasms, and polyps. Tamoxifen-related polyps are characteristically multiple and fibrotic. A variety of metaplasias and periglandular stromal condensation may be seen. Relatively few articles have focused on the descriptive morphology of the full range of tamoxifen-associated lesions. The present study further defines the histologic features in both endometrial polyps and nonpolyp endometrium. One hundred and two specimens (including 50 polyps) were reviewed using hormone replacement therapy-related endometrial specimens and conventional polyps as the control groups. The most characteristic findings of tamoxifen-associated lesions included polarized glands along the long axis of polyps (40%), a cambium layer (72%), frequent and diverse metaplasias, staghorn glands (36%), myxoid degeneration (12%), and small glands (36%). Similar morphologic features were identified in the hormone replacement therapy and control groups but to a variable, lesser extent. Overall, the tamoxifen group consisted of 18 cases of hyperplasia (11 complex, 7 simple) and one case each of adenofibroma, adenosarcoma, endometrial stromal sarcoma, and leiomyosarcoma. Although none of the features is diagnostic, the presence of diverse metaplasias, polarized glands, staghorn glands, and a cambium layer strongly suggest tamoxifen exposure especially if a number of these features are present concurrently within the same material.

Adult↗
PubMed1998

Identification of HHV8 in early Kaposi's sarcoma: implications for Kaposi's sarcoma pathogenesis.

AIMS: Kaposi's sarcoma is a vascular tumour of uncertain pathogenesis possibly caused by an infectious agent, identified in high risk groups. Accumulating solution phase polymerase chain reaction (PCR) and seroepidemiological data suggest that a previously undescribed herpes DNA virus (human herpesvirus 8 (HHV8)) is the causative agent. Using a unique cohort of early Kaposi's sarcoma, the precise cell type infected with HHV8 in such lesions was identified to elucidate further the role of HHV8 in the pathobiology of Kaposi's sarcoma. METHODS: Sixteen cases of early Kaposi's sarcoma (derived from skin and lymph node) were assessed for the presence of HHV8 using both standard solution phase PCR and TaqMan PCR to the KS330 Bam region of HHV8. In situ amplification was also performed on a selected group in an attempt to identify the candidate infected cells. RESULTS: Using both conventional solution phase and TaqMan PCR, 87% of cases were positive. In addition, HHV8 amplicons were localised in situ to endothelial and spindle cell proliferations in early Kaposi's sarcoma. The HHV8 viral load varied from lesion to lesion. CONCLUSIONS: The presence of HHV8 in early lesions supports a role for HHV8 in the pathogenesis of Kaposi's sarcoma. Coupled with recent seroepidemiological studies, these results suggest that HHV8 is the aetiological agent of Kaposi's sarcoma. Its precise interaction with other factors known to be involved in the development of Kaposi's sarcoma, including cytokines and anti-apoptosis genes, requires elucidation.

Adolescent↗
PubMed1998

Human herpes virus 8 (HHV-8) in Kaposi's sarcoma: lack of association with Bcl-2 and p53 protein expression.

AIMS: Human herpes virus 8 (HHV-8) is the infectious agent implicated in the pathogenesis of Kaposi's sarcoma, although its mode of action is unclear. Recent work indicates that the HHV-8 genome encodes a viral Bcl-2 homologue (v-Bcl-2). The aim of this study was to explore Bcl-2 expression in Kaposi's sarcoma using a unique set of HHV-8 positive and negative cases, and to determine whether there is a relation with p53 expression. METHODS: Up to 18 specimens from 17 patients were selected. HHV-8 status was determined using nested polymerase chain reaction (PCR) to the open reading frame (ORF) 26, with further confirmation by TaqMan PCR. In addition, Bcl-2 and p53 immunohistochemistry were performed using standard protocols. RESULTS: The results suggest that Bcl-2 and p53 expression is independent of HHV-8 status. In addition, there does not appear to be a direct correlation with disease stage. CONCLUSIONS: HHV8 histopathogenesis is likely to be a multifactorial complex process, which may be mediated in part by viral genes and apoptosis regulating homologues.

Female↗
PubMed1998

Partial regression in primary carcinoma of the lung: does it occur?

AIMS: To study immunohistochemically a group of 28 primary lung cancers which demonstrated histological features reminiscent of those characteristic of regression in malignant melanoma, to determine the phenotype of their immune cell infiltrates. METHODS AND RESULTS: Using a standard s-ABC immunoperoxidase method then quantification by the Leica Q500 MC image analyser, the cellular infiltrate in these tumours, when compared to 67 control cases, showed excess CD3 + T lymphocytes (P < 0.007), with an increase in CD4:CD8 ratio and increased CD68 + macrophages (P = 0.00001). CD57 + natural killer cells and S100 + Langerhans cells were also increased, but not quite significantly (P = 0.048 and P = 0.072, respectively). CONCLUSIONS: This immunophenotype resembles that shown in regressing skin malignancies and suggests a similar process occurring in lung cancer. Regressing lung cancers are associated with a better prognosis than matched controls (P = 0.0034), some showed radiological evidence of growth retardation and the group had an excess of the large cell undifferentiated histological type.

Antigens, CD↗
PubMed1998

Influenza viral infections: presentation, prevention, and treatment.

Each year, 20,000 to 40,000 people in the United States die of influenza and associated complications. Influenza infections account for several billion dollars in health care expenditures each year. Two important measures to minimize the incidence of influenza infection are vaccination and chemoprophylaxis with antiviral agents. Vaccinations must be given annually for two reasons: the antigenic changes that influenza strains, particularly influenza A, undergo and the diminished antibody response that occurs over time. Specific efforts should be targeted to high-risk groups. The adverse effects of the vaccine are generally mild, with a sore arm being the most common complaint. Chemoprophylaxis is the recommended substitute for vaccination in people with egg allergy. The vaccine is effective 70% to 90% of the time in preventing illness in healthy individuals. Unfortunately, less than 30% of the targeted population receives the vaccination each year. More research must be conducted on ways to improve the organization and administration of influenza vaccinations.

Antigenic Variation↗
PubMed1997

HHV8 and female Kaposi's sarcoma.

Kaposi's sarcoma (KS) is an enigmatic tumour of uncertain histogenesis. Epidemiological data have long suggested that KS may be caused by an infectious agent, possibly sexually transmitted. Following the documentation of human herpesvirus 8 (HHV8) and its strong association with all forms of KS, it now appears that the putative agent has at last been identified. As KS is rare in females, a unique group was screened for the presence of HHV8 using both conventional solution-phase polymerase chain reaction (PCR) and the newly described technique of TaqMan PCR. The presence of HHV8 was demonstrated in 10/12 of these female patients. This further supports the direct role of HHV8, in conjunction with cytokines and other factors, in the pathogenesis of KS.

Adolescent↗
PubMed1997

p53, c-erbB-2 and nm23 expression have no prognostic significance in primary pulmonary adenocarcinoma.

OBJECTIVE: We analysed nm23, c-erbB-2 and p53 protein expression in lung adenocarcinoma in relation to clinicopathological status and patient survival, to elucidate any potential prognostic value. Published reports suggest that high p53 and c-erbB-2 protein expression and loss of nm23 protein expression are associated with poor prognosis. METHODS: A total of 162 pulmonary adenocarcinomas resected between 1980 and 1991 were stained using monoclonal antibodies to nm23 (NCL-nm23), c-erbB-2 (NCL-CB11) and p53 (DAKO Do7). Antigen retrieval was by microwave heating and bound antibody was visualised using standard immunohistochemical methods. Staining was scored by two observers blinded to tumour status and patient survival. RESULTS: Of the tumours, 101/162 (62.3%) exhibited high-level p53 expression, 30 (18.5%) showed high-level c-erbB-2 membrane staining, and 77 (47.5%) demonstrated loss of nm23 positivity. The influence of T and N status and disease stage on postoperative survival was as expected. The predicted effect on patient survival of nm23, c-erbB-2 or nm23 protein expression suggested by previous studies was not verified by our work. This was true both overall and for groups within the same T or N status or stage. CONCLUSION: Immunohistochemical assessment of the nm23, c-erbB-2 and p53 proteins using the above monoclonal antibodies does not have value as an independent prognostic indicator in pulmonary adenocarcinoma.

Adenocarcinoma↗