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P Maxwell

Publications and source records attributed to P Maxwell.

At least 37 records · Page 2Linked to original sources
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

CD10 is a sensitive and diagnostically useful immunohistochemical marker of normal endometrial stroma and of endometrial stromal neoplasms.

AIMS: The CD10 antigen is expressed in acute lymphoblastic leukaemia and follicle centre cell lymphoma. A recent study investigating the expression of CD10 in a wide range of non-haematopoietic neoplasms found positive staining in a small number of endometrial stromal sarcomas as well as in normal endometrial stroma. The present study aimed to ascertain whether CD10 positivity is indeed found in normal endometrial stroma and endometrial stromal neoplasms. Staining of a range of tumours which can be confused morphologically with endometrial stromal neoplasms was also undertaken to ascertain whether antibodies against CD10 are of value in a diagnostic sense. METHODS AND RESULTS: Neoplasms included in the study were endometrial stromal nodule (n=1), low-grade endometrial stromal sarcoma (ESS) (n=13), high-grade ESS (n=6), mixed endometrial stromal-smooth muscle tumour (n=1), uterine cellular leiomyoma (n=10), uterine leiomyosarcoma (n=5), adult granulosa cell tumour (AGCT) (n=10), undifferentiated endometrial carcinoma (n=6), uterine carcinosarcoma with an endometrial stromal component (n=1) and type II uterine mesenchymal tumour with sex cord-like elements (n=1). Cases of proliferative (n=5), secretory (n=5) and atrophic (n=3) endometrium were also stained. There was positive staining of stroma but not of glands in all cases of non-tumorous endometrium. There was positive staining of the endometrial stromal nodule and of all low-grade ESS. Staining in these varied but was often diffuse and of moderate to strong intensity. There was positive staining of four of six high-grade ESS, but this was usually focal. There was also positive staining of the endometrial stromal component in the mixed endometrial stromal-smooth muscle tumour and in the uterine carcinosarcoma. Most cellular leiomyomas were completely negative although three exhibited weak positivity. There was some positivity, usually focal or weak, of three of five leiomyosarcomas. Most AGCT and undifferentiated carcinomas were completely negative although one case of each exhibited focal staining. There was focal staining of the type II uterine mesenchymal tumour with sex cord-like elements. CONCLUSION: CD10 is a reliable and sensitive immunohistochemical marker of normal endometrial stroma. Positivity, which is often strong and/or diffuse is found in endometrial stromal nodules and low-grade ESS. Positive staining with CD10, when strong and diffuse, may be useful in distinguishing these tumours from histological mimics, especially cellular leiomyoma and AGCT which are generally negative. In this situation, CD10 should be used as part of a panel which might include desmin and alpha-inhibin depending on the differential diagnosis considered. Positive staining with CD10 in a high-grade uterine sarcoma which is negative with muscle markers might indicate endometrial stromal differentiation and identify a group of neoplasms which it is correct to diagnose as high-grade ESS rather than undifferentiated uterine sarcoma.

Endometrial Neoplasms↗
PubMed2001

Thyroglobulin immunoreactivity in lymph node histiocytes: a potential diagnostic pitfall.

AIMS: Strong thyroglobulin immunoreactivity within sinus histiocytes in a lymph node draining a papillary thyroid carcinoma was observed in a recent case. This prompted the investigation of whether thyroglobulin immunoreactivity is common in regional lymph nodes in cases of thyroid malignancy. METHODS: Eighty seven lymph nodes were studied from 21 cases of thyroid malignancy. These comprised papillary carcinoma (n = 12), follicular carcinoma (n = 4), medullary carcinoma (n = 3), and one case each of squamous and anaplastic carcinoma. Eleven cervical lymph nodes from patients with no evidence of thyroid disease were included as controls. Sections were stained with a monoclonal antibody against thyroglobulin. RESULTS: In the cases of thyroid malignancy, 32 of 87 lymph nodes showed positive staining for thyroglobulin of histiocytes within the subcapsular and medullary sinuses. In an additional four cases, there was positive staining of lymph within lymphatic channels. Positivity was present in at least one node in 15 of 21 cases. There was no positivity in the control cases. There was no correlation between the size of the primary tumour and the presence of thyroglobulin positivity. CONCLUSIONS: Positive staining with antithyroglobulin occurs not uncommonly in sinus histiocytes in lymph nodes draining thyroid tumours. This positivity could be the result of the destruction of normal thyroid follicles, with the release of thyroglobulin, which is taken up by histiocytes, which subsequently drain to local lymph nodes. Pathologists should be aware of this phenomenon and should be careful not to interpret this as metastatic tumour.

Biomarkers↗
PubMed2001

The effect of antisense Bcl-2 oligonucleotides on Bcl-2 protein expression and apoptosis in human bladder transitional cell carcinoma.

PURPOSE: Bcl-2 is an important determinant of transitional cell carcinoma of the bladder recurrence and progression as well as a factor in patient response to chemotherapy or radiotherapy. We determined Bcl-2 down-regulation after antisense oligonucleotide therapy and synergism with mitomycin C in transitional cell carcinoma of the bladder. MATERIALS AND METHODS: Bcl-2 protein was quantified using flow cytometry and immunohistochemistry in 4 bladder cancer cell lines, in bladder washings from 6 patients with carcinoma in situ and in 16 patient tumor samples. The synergistic effects of antisense oligonucleotides G3139 and 2009, and mitomycin C were investigated in 4 cell lines, while 2009 down-regulation was examined in 20 tumor explants in an ex vivo model. RESULTS: Bcl-2 protein expression was found in all 4 cell lines and in 5 of the 6 cell populations derived from patients with carcinoma in situ. Of the 16 tumors 7 were classified positive by frozen section immunohistochemistry and quantitative flow cytometry. G3139 and 2009 down-regulated Bcl-2 protein expression in all 4 cell lines and 2009 down-regulated Bcl-2 protein expression in half of the Bcl-2 positive tumor specimens. There was only evidence in 1 cell line, T24/83, that Bcl-2 protein expression down-regulation enhanced mitomycin C induced apoptotic cell death. CONCLUSIONS: Bcl-2 was expressed in a significant proportion of bladder tumors and in carcinoma in situ. Therefore, antisense oligonucleotides represent a viable strategy for Bcl-2 protein down-regulation. However, it may not always translate into an increased level of mitomycin C induced apoptosis in transitional cell carcinoma of the bladder.

Apoptosis↗
PubMed2001

Characterization of a thymidylate synthase (TS)-inducible cell line: a model system for studying sensitivity to TS- and non-TS-targeted chemotherapies.

Thymidylate synthase (TS) is responsible for the de novo synthesis of thymidylate, which is required for DNA synthesis and repair and which is an important target for fluoropyrimidines such as 5-fluorouracil (5-FU), and antifolates such as Tomudex (TDX), ZD9331, and multitargeted antifolate (MTA). To study the importance of TS expression in determining resistance to these agents, we have developed an MDA435 breast cancer-derived cell line with tetracycline-regulated expression of TS termed MTS-5. We have demonstrated that inducible expression of TS increased the IC(50) dose of the TS-targeted therapeutic agents 5-FU, TDX, and ZD9331 by 2-, 9- and 24-fold respectively. An IC(50) dose for MTA was unobtainable when TS was overexpressed in these cells, which indicated that MTA toxicity is highly sensitive to increased TS expression levels. The growth inhibitory effects of the chemotherapeutic agents CPT-11, cisplatin, oxaliplatin, and Taxol were unaffected by TS up-regulation. Cell cycle analyses revealed that IC(50) doses of 5-FU, TDX and MTA caused an S-phase arrest in cells that did not overexpress TS, and this arrest was overcome when TS was up-regulated. Furthermore, the S-phase arrest was accompanied by 2- to 4-fold increased expression of the cell cycle regulatory genes cyclin E, cyclin A, and cyclin dependent kinase 2 (cdk2). These results indicate that acute increases in TS expression levels play a key role in determining cellular sensitivity to TS-directed chemotherapeutic drugs by modulating the degree of S-phase arrest caused by these agents. Moreover, CPT-11, cisplatin, oxaliplatin, and Taxol remain highly cytotoxic in cells that overexpress TS.

Blotting, Northern↗
PubMed2000

The macrophage - a novel system to deliver gene therapy to pathological hypoxia.

The use of activated macrophages in the treatment of cancer has been largely ineffectual. By 'arming' these cells with the ability to express a therapeutic gene we demonstrate significant advances in the efficacy of this approach. We have used a hypoxia-regulated adenoviral vector to transduce human macrophages with either a reporter or a therapeutic gene encoding human cytochrome P4502B6 (CYP2B6). Infiltration of transduced macrophages into a tumour spheroid results in induction of gene expression. We demonstrate significant tumour cell killing only in the presence of cyclophosphamide via activation by P4502B6 and show that this can be further targeted to tumours through hypoxia regulated gene expression. Gene Therapy (2000) 7, 255-262.

Adenoviridae↗
PubMed2000

Bcl-2 expression in sequential biopsies of potentially malignant oral mucosal lesions assessed by immunocytochemistry.

OBJECTIVE: To examine, for the first time Bcl-2 expression in sequential (autogenous) oral mucosal biopsies taken from the same sites in a gender, risk-factor matched, Caucasoid sample, over a 21-year period. DESIGN: Retrospective immunocytochemical longitudinal study of archival serial biopsies. MATERIALS AND METHODS: Computer records were used to identify biopsy specimens derived from 12 patients. These were divided into four groups: (1) Histologically innocuous lesions which remained histologically innocuous. (2) Dysplastic lesions which remained dysplastic. (3) Histologically innocuous lesions which later progressed to squamous cell carcinoma (SCC). (4) Dysplastic lesions which later progressed to SCC. This represented 65 biopsies in total. Bcl-2 expression was studied using mouse antihuman BCL-2 oncoprotein clone 124 (Dako, Denmark). RESULTS: Generally, there was a lack of Bcl-2 immunoreactivity in the epithelium, with one exception in dysplastic epithelium from a group (3) patient. CONCLUSION: These findings suggest that in our series, Bcl-2 is not expressed early in oral premalignant lesions and appears to contradict previous reports. Possible explanations for this disparity are considered.

Adult↗
PubMed2000

Audit and internal quality control in immunohistochemistry.

AIMS: Although positive and negative controls are performed and checked in surgical pathology cases undergoing immunohistochemistry, internal quality control procedures for immunohistochemistry are not well described. This study, comprising a retrospective audit, aims to describe a method of internal quality control for immunohistochemistry. A scoring system that allows comparison between cases is described. METHODS: Two positive tissue controls for each month over a three year period (1996-1998) of the 10 antibodies used most frequently were evaluated. All test cases undergoing immunohistochemistry in the months of April in this three year period were also studied. When the test case was completely negative for a given antibody, the corresponding positive tissue control from that day was examined. A marking system was devised whereby each immunohistochemical slide was assessed out of a possible score of 8 to take account of staining intensity, uniformity, specificity, background, and counterstaining. Using this scoring system, cases were classified as showing optimal (7-8), borderline (5-6), or unacceptable (0-4) staining. RESULTS: Most positive tissue controls showed either optimal or borderline staining with the exception of neurone specific enolase (NSE), where most slides were unacceptable or borderline as a result of a combination of low intensity, poor specificity, and excessive background staining. All test cases showed either optimal or borderline staining with the exception of a single case stained for NSE, which was unacceptable. CONCLUSIONS: This retrospective audit shows that immunohistochemically stained slides can be assessed using this scoring system. With most antibodies, acceptable staining was achieved in most cases. However, there were problems with staining for NSE, which needs to be reviewed. Laboratories should use a system such as this to evaluate which antibodies regularly result in poor staining so that they can be excluded from panels. Routine evaluation of immunohistochemical staining should become part of everyday internal quality control procedures.

Humans↗
PubMed2000

Aggressive angiomyxoma of pelvic parts exhibits oestrogen and progesterone receptor positivity.

AIMS: Aggressive angiomyxoma of pelvic parts is a distinctive soft tissue tumour that chiefly involves the vulvar and perineal region of female patients. Several previous reports have demonstrated oestrogen receptor (ER) and/or progesterone receptor (PR) positivity in this neoplasm. The aim of this study was to confirm whether ER and/or PR positivity is present in aggressive angiomyxoma. We also wished to ascertain whether positivity may be found in the stromal cells of normal vulval skin and in other lesions at this site that can cause diagnostic confusion with aggressive angiomyxoma. METHODS: Five aggressive angiomyxomas in female patients and one involving male pelvic soft parts were stained immunohistochemically with antibodies against ER and PR. Other samples studied were normal vulval skin (n = 7), fibroepithelial polyps of vulva (n = 7), vulval smooth muscle neoplasms (n = 5), vulval nerve sheath tumours (n = 2), vaginal angiomyofibroblastoma (n = 1), and pelvic myxoma (n = 1). Nuclear staining was classified as negative, weak, moderate, or strong and the proportion of positively staining cells was categorised as 0, < 10%, 10-50%, or > 50%. RESULTS: All five cases of aggressive angiomyxoma in female patients were positive for ER (two with weak intensity involving < 10% of cells and three with moderate intensity involving 10-50% of cells) and four of five cases were strongly positive for PR in > 50% of cells. The other case was negative for PR. There was no staining with antibodies to ER or PR in the single male patient with aggressive angiomyxoma. Other samples exhibiting positivity of the stromal cells for either ER or PR were normal vulval skin (five of seven, ER; two of seven, PR), fibroepithelial polyps (four of seven, ER; five of seven, PR), smooth muscle neoplasms (three of five, ER; four of five, PR), nerve sheath tumours (one of two, ER; one of two, PR), angiomyofibroblastoma (one of one, ER; one of one, PR), and pelvic myxoma (one of one, PR). CONCLUSIONS: All cases of aggressive angiomyxoma of pelvic soft parts in female patients exhibited positivity for ER and/or PR. Because of its propensity to occur in female patients during the reproductive years, it is possible that aggressive angiomyxoma is a hormonally responsive neoplasm. However, dermal fibroblasts in normal vulval skin and stromal cells in a variety of vulval lesions can also be positive. ER or PR immunoreactivity cannot be used to distinguish aggressive angiomyxoma and its histological mimics.

Biomarkers, Tumor↗
PubMed2000

Enzyme-linked immunosorbent assay for the diagnosis of bovine leukosis: comparison with the agar gel immunodiffusion test approved by the Canadian Food Inspection Agency.

Four commercially available bovine leukemia virus (BLV)-ELISA kits from Europe or the United States were compared to the agar gel immunodiffusion (AGID) test officially approved by the Canadian Food Inspection Agency (CFIA). A total of 1200 cattle serum samples were used. Three ELISA kits based on the envelope glycoprotein (gp51) gave an excellent correlation with the AGID test. The kappa values were 0.998, 0.984, and 0.986 for the ELISA kits #1, #2, and #3, respectively. The ELISA kit based on the p24 core protein was found to be less sensitive than the officially approved AGID test and detected 5.13% of false negatives. Forty BLV AGID strongly positive serum samples were diluted. Based on the dilution experiment, the gp51 ELISA kits were found to be more sensitive than the AGID test kits. They were capable of detecting antibodies in samples diluted up to 1/5000 (kit #1), 1/20 800 (kit #2) and 1/4000 (kit #3), whereas the AGID kit was only capable of detecting antibodies in samples diluted up to 1/100. Based on these observations, the gp51 BLV-ELISA was recognized as an official test method for the serodiagnosis of bovine leukosis in Canada.

Agar↗
PubMed1999

Changes in the secretion of insulin-like growth factor binding proteins -2 and -4 associated with the development of tamoxifen resistance and estrogen independence in human breast cancer cell lines.

We investigated the secretion of insulin-like growth factor binding proteins (IGFBPs) by estrogen-dependent ZR-75-1 and MCF-7 human breast cancer cells, and tamoxifen-resistant (ZR-75-9a1 and LY2) and estrogen-independent (ZR-PR-LT) variants which express altered levels of IGF-I receptor. IGFBP species (35 kDa and 44 kDa) were detectable in conditioned serum-free medium (SFM) by immunoblotting and positively identified as IGFBP-2 and -3, respectively. Secretion of IGFBP-2 into SFM by the tamoxifen-resistant and estrogen-independent cell lines was markedly reduced and secretion into SFM of the 24-kDa species, assigned the identity of IGFBP-4, was also reduced in the tamoxifen-resistant lines. There was no clear correlation between patterns of IGFBP secretion and IGF-I receptor expression.

Antineoplastic Agents, Hormonal↗
PubMed1999

Interphase cytogenetics of chromosomes 11 and 17 in fine needle aspirates of breast cancer.

The aims of this investigation were to compare quantitative with qualitative analysis of fluorescent in situ hybridization (FISH) centromere signals in interphase breast cancer cell nuclei and to evaluate the possible clinical utility of detecting numerical abnormalities of chromosomes 11 and 17 by FISH in the preoperative prediction of breast cancer histological grade. Commercial digoxigenin-labeled centromere probes to chromosomes 11 and 17 were hybridized to 69 malignant aspirates with histological follow-up. Aspirates were categorized as disomic or aneusomic for chromosomes 11 and 17 qualitatively; a subset of aspirates was also analyzed quantitatively. The quantitative and qualitative approaches resulted in almost identical categorisation. There was a significant association between the qualitative categorization of aspirates as aneusomic or disomic, the histological grade of the excised tumours (P = .0695, n = 69), and the cytological grade of the clinical aspirates (P = .006, n = 35). Although histological grade III tumors were almost invariably polysomic for one or both chromosomes, polysomy was also detected in grade I and II tumors. Qualitative FISH analysis was shown to be more sensitive than cytological grading in predicting histological grade III but was of lower specificity and was therefore not clinically useful.

Adult↗
PubMed1999

Outcome following haemodialysis catheter-related Staphylococcus aureus bacteraemia.

Staphylococcus aureus is a frequent cause of haemodialysis access-related bacteraemia. The propensity for this organism to seed from the bloodstream to distant sites is well recognized, but the rate at which this occurs is poorly defined in patients with removable haemodialysis catheters. This retrospective study identified 47 patients with 50 episodes of S. aureus haemodialysis catheter-related bacteraemia between August 1993 and December 1995. Adverse events were recorded until February 1996. Thirty of 50 episodes (60%) were apparently uncomplicated. Bacterial seeding to heart valves or distant sites was documented in eight episodes (16%), of which six occurred during antibiotic therapy. A further 12 patients had persistent bacteraemia in the absence of a defined focus of infection, the last positive blood culture ranging from 2-19 days (mean 6.6, median 5) after removal of the haemodialysis catheter and commencing appropriate antibiotic treatment. The serious nature of this infection confirms the need for prevention, together with effective strategies for investigation and treatment in this patient population.

Adult↗
PubMed1999

High metallothionein expression is associated with features predictive of aggressive behaviour in endometrial carcinoma.

AIMS: Metallothioneins (MTs) are a group of ubiquitous low molecular weight proteins with a high affinity for heavy metal ions. The aim of the present study was to investigate MT expression in a series of endometrial carcinomas. We wished to determine whether MT expression in endometrial carcinoma was related to established prognostic factors such as tumour grade, stage and histological type. We also wanted to establish if high MT expression in curettings of endometrial carcinoma was predictive of high expression in the subsequent hysterectomy specimen. METHODS AND RESULTS: Sixty-three cases of endometrial carcinoma were included in the study. These comprised 57 endometrioid adenocarcinomas (15 grade 1, 25 grade 2, 17 grade 3), three papillary serous adenocarcinomas, two mucinous adenocarcinomas and one clear cell adenocarcinoma. Forty-five tumours were stage I, 10 were stage II and eight were stage III. In 28 cases, diagnostic endometrial curettings, performed prior to hysterectomy, were available for study. Immunohistochemical staining was performed using the anti-MT monoclonal antibody E9. The intensity and distribution of MT staining were assessed using a semiquantitative method. This resulted in an intensity distribution (ID) score out of a maximum of 300. The mean ID score of grade 1 and 2 endometrioid adenocarcinomas was 67 and 63, respectively, while for grade 3 tumours the mean ID score was 114. This was statistically significant (P = 0.05). The three papillary serous adenocarcinomas had high ID scores with a mean of 208. The mean ID score of stage I tumours was 69. This was lower than those of stage II and III tumours which had mean ID scores of 116 and 128, respectively. However, these differences were not statistically significant (P = 0.288). A significant correlation was observed between MT ID scores in endometrial curettings and in the subsequent hysterectomy (P = 0.013). CONCLUSIONS: MT isoforms can be demonstrated in most endometrial adenocarcinomas. High MT ID scores are associated with high grade and high stage endometrial adenocarcinomas and with the aggressive papillary serous adenocarcinoma. Whether this is of value as an independent prognostic factor has yet to be established.

Adenocarcinoma↗
PubMed1999

Adenocarcinomas of various sites may exhibit immunoreactivity with anti-inhibin antibodies.

AIMS: The aim of this study was to investigate the immunohistochemical staining of adenocarcinomas arising primary at a variety of sites with antibodies against the alpha and beta subunits of human inhibin. We wished to determine whether positivity in an adenocarcinoma is specific for an ovarian primary. METHODS AND RESULTS: Seventy-eight adenocarcinomas were stained with the commercially available monoclonal antibodies R1 and E4 which react against the alpha and betaA subunits of human inhibin, respectively. In 20 adenocarcinomas, there was positivity with R1 and 46 cases were immunoreactive with E4. Positive staining was generally weak although there was strong reactivity with R1 in five cases and with E4 in two cases. CONCLUSIONS: Positive staining with antibodies against the alpha and beta subunits of inhibin may be present in adenocarcinomas arising primary at a variety of sites. Caution should be exercised when using anti-inhibin antibodies to distinguish between an ovarian carcinoma and a sex cord-stromal tumour. These antibodies should always be used as part of a panel. Positivity with anti-inhibin antibodies in an adenocarcinoma is not specific for an ovarian primary.

Adenocarcinoma↗