MUC1: Antibodies and immunoassays

High molecular weight mucins represent a unique challenge as tumor markers by virtue of their complex array of epitopes, The list is dominated by the high molecular weight mucins MUC1, CEA and CA125. While the currently accepted role for these tumor markers is in the prediction and detection of relapse, it is possible that their sensitivity and specificity can be improved. Although immunoassays detecting the tumor marker MUC1 are both sensitive and specific for predicting relapse in breast cancer, so far they are not in widespread use in the follow-up of this disease. Are there new combinations of conventional reagents that could improve assay sensitivity, or should we be looking for more radical changes in assay design incorporating combinatorial technology? Copyright (C) 2001 S. Karger AG, Basel.

Primary fallopian tube carcinoma: the Queensland experience

The purpose of this study was to review the experience with fallopian tube carcinoma in Queensland and to compare it with previously published data. Thirty-six patients with primary fallopian tube carcinoma treated at the Queensland Gynaecological Cancer Center from 1988 to 1999 were reviewed in a retrospective clinicopathologic study. All patients had primary surgery and 31/36 received chemotherapy postoperatively. Abnormal vaginal bleeding (15/36) and abdominal pain (14/36) were the most common presenting symptoms at the time of diagnosis. Median follow-up was 70.3 months and the median overall survival was 68.1 months. Surgical stage I disease (P = 0.02) and the absence of residual tumor after operation (P = 0.03) were the only factors associated with improved survival. Twenty of the 36 patients (55%) presented with stage I disease and survival was 62.7% at 5 years. No patient with postoperative residual tumor survived. The majority of the patients with fallopian tube carcinoma present with stage I disease at diagnosis, but their survival probability is low compared with that of other early stage gynecological malignancies. If primary surgical debulking cannot achieve macroscopic tumor clearence, the chance of survival is extremely low.

Accuracy of frozen section for the operative management of endometrial cancer

Objective To assess the accuracy of intra-operative frozen section reports at identifying the features of high risk uterine disease compared with final histopathology. Design Retrospective study. Methods The records, of 460 patients with uterine cancer registered with the Queensland Centre for Gynaecological Cancer between January 1, 1996 and December 31, 1998 were reviewed. Intra-operative frozen section was undertaken in 260 patients with endometrial adenocarcinoma. Frozen section pathology was compared with the final histopathology reports. Inter-observer reliability was assessed using percentage agreement and kappa statistics. Clinical notes were also reviewed to determine if errors resulted in sub-optimal patient care. Results Respectively, tumour grade and depth of myometrial invasion were accurately reported in 88.6% of cases (expected 61.5%, Kappa 0.70) and 94.7% (expected 53.8%, Kappa 0.89). Errors were predominantly attributable to difficulties with respect to the interpretation of tumour grade. The error resulted in the patient receiving sub-optimal surgical management in only I I cases (5.3%) Conclusion Frozen section is accurate at identifying the features of high risk uterine disease in the setting of endometrial cancer and can play an important role in directing primary operative management.

Apoptosis and cell proliferation in the development of gastric carcinomas: Associations with c-myc and p53 protein expression

Background and Aim: Patients with gastric carcinomas have a poor prognosis and low survival rates. The aim of the present paper was to characterize cellular and molecular properties to provide insight into aspects of tumor progression in early compared with advanced gastric cancers. Methods: One hundred and nine graded gastric carcinomas (early or advanced stage, undifferentiated or differentiated type) with paired non-cancer tissue were studied to define the correlation between apoptosis (morphology, terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labeling), cell proliferation (Ki-67 expression, morphology) and expression and localization of two proteins frequently having altered expression in cancers, namely p53 and c-myc. Results: Overall, apoptosis was lower in early stage, differentiated and undifferentiated gastric carcinomas compared with advanced-stage cancers. Cell proliferation was comparatively high in all stages. There was a high level of p53 positivity in all stages. Only the early- and advanced-stage undifferentiated cancers that were p53 positive had a significantly higher level of apoptosis (P< 0.05). Cell proliferation was significantly greater (P < 0.05) only in the early undifferentiated cancers that had either c-myc or p53-positivity. Conclusions: The results indicate that low apoptosis and high cell proliferation combine to drive gastric cancer development. The molecular controls for high cell proliferation of the early stage undifferentiated gastric cancers involve overexpression of both p53 and c-myc. Overexpression of p53 may also control cancer development in that its expression is associated with higher levels of apoptosis in early and late-stage undifferentiated, cancers. (C) 2002 Blackwell Publishing Asia Pty Ltd.

Expression analysis of delta-catenin and prostate-specific membrane antigen: Their potential as diagnostic markers for prostate cancer

The current approach to prostate cancer diagnosis has major limitations including the inability of prostate-specific antigen (PSA) assays to accurately differentiate between prostate cancer and benign prostate hyperplasia (BPH) and the imprecision of transrectal ultrasound (TRUS) biopsy sampling. We have employed cDNA microarray screening to compare gene expression patterns in BPH and tumour samples to identify expression markers that may be useful in discriminating between these conditions. Screening of 3 individual cDNA arrays identified 8 genes with expression 3-fold greater in 6 tumour tissues than in 1 nontumour sample and I BPH sample. Real-time PCR was used to confirm the overexpression of these 8 genes and 12 genes selected from the literature against a panel of 17 tumours and I 1 BPH samples. Two genes, delta-catenin (delta-catenin; CTNND2) and prostate-specific membrane antigen (PSMA; FOLH1), were significantly overexpressed in prostate cancer compared to BPH. Prostate epithelial cells stained positively for S-catenin and PSMA in our prostate cancer tissues, whereas the majority of our BPH tissues were negative for both markers. Thus we have identified delta-catenin (not previously associated with prostatic adenocarcinoma) and confirmed the potential of PSMA as potential candidates for the diagnosis and management of prostate cancer. (C) 2002 Wiley-Liss. Inc.

The impact of positive peritoneal washings and serosal and adnexal involvement on survival in patients with stage IIIA uterine cancer

Objective. The aim of this study was to determine the prognostic significance of serosal involvement (SER), adnexal involvement (ADN), and positive peritoneal washings (PPW) in patients with Stage IIIA uterine cancer. We also sought to determine patterns of recurrence in patients with this disease. Methods. The records of 136 patients with Stage IIIA uterine cancer treated at the Queensland Centre for Gynecological Cancer between March 1983 and August 2001 were reviewed. One hundred thirty-six patients underwent surgery and 58 (42.6%) had full surgical staging. Seventy-five patients (55.2%) had external beam radiotherapy and/or brachytherapy postoperatively. Overall survival was the primary statistical endpoint. Statistical analysis included univariate and multivariate Cox models. Results. Forty-six patients (33.8%) had adnexal involvement, 23 (16.9%) had serosal involvement, and 40 (29.4%) had positive peritoneal washings. Median follow-up was 55.1 months (95% confidence interval, 36.9 to 73.4 months) after which time 71 patients (52.2%) remained alive. For patients with endometrioid adenocarcinoma, ADN and SER were associated with impaired survival on multivariate analysis (odds ratio 2.8 and 3.2, respectively). In the subgroup of patients with high-risk tumors (including papillary serous carcinomas, clear cell carcinomas, and uterine sarcomas), neither ADN, nor SER, nor PPW influenced survival. Conclusion. Patients with Stage IIIA uterine cancer constitute a heterogeneous group. For patients with endometrioid adenocarcinoma, both ADN and SER, but not PPW, were associated with impaired prognosis. For patients with high-risk histological types, prognosis is poor for all three factors. (C) 2002 Elsevier Science (USA).

Decreased expression of the Id3 gene at 1p36.1 in ovarian adenocarcinomas

The molecular events that drive the initiation and progression of ovarian adenocarcinoma are not well defined. We have investigated changes in gene expression in ovarian cancer cell lines compared to an immortalized human ovarian surface epithelial cell line (HOSE) using a cDNA array. We identified 17 genes that were under-expressed and 10 genes that were over-expressed in the cell lines compared to the HOSE cells. One of the genes under-expressed in the ovarian cancer cell lines, Id3, a transcriptional inactivator, was selected for further investigation. Id3 mRNA was expressed at reduced levels in 6 out of 9 ovarian cancer cell lines compared to the HOSE cells while at the protein level, all 7 ovarian cancer cell lines examined expressed the Id3 protein at greatly reduced levels. Expression of Id3 mRNA was also examined in primary ovarian tumours and was found in only 12/38 (32%) cases. A search was conducted far mutations of Id3 in primary ovarian cancers using single stranded conformation polymorphism (SSCP) analysis. Only one nucleotide substitution, present also in the corresponding constitutional DNA, was found in 94 ovarian tumours. Furthermore no association was found between LOH at 1p36 and lack of expression of Id3. These data suggest that Id3 is not the target of LOH at 1p36. (C) 2001 Cancer Research Campaign.

Fas ligand and tumour counter-attack in colorectal cancer stratified according to microsatellite instability status

Expression of membrane-bound Fas ligand (FasL) by colorectal cancer cells may allow the development of an immune-privileged site by eliminating incoming tumour-infiltrating lymphocytes (TILs) in a Fas-mediated counter-attack. Sporadic colorectal cancer can be subdivided into three groups based on the level of DNA microsatellite instability (NISI). High-level NISI (NISI-High) is characterized by the presence of TILs and a favourable prognosis, while microsatellite-stable (MSS) cancers are TIL-deficient and low-level MSI (MSI-Low) is associated with an intermediate TIL density. The purpose of this study was to establish the relationship between MSI status and FasL expression in primary colorectal adenocarcinoma. Using immunohistochemistry and a selected series of 101 cancers previously classified as 31 MSI-High, 30 NISI-Low, and 40 MISS, the present study sought to confirm the hypothesis that increased TIL density in MSI-High cancers is associated with low or absent membrane-bound FasL expression, while increased FasL in MSS cancers allows the killing of host TILs. TUNEL/CD3 double staining was also used to determine whether MSS cancers contain higher numbers of apoptotic TILs in vivo than MSI-High or MSI-Low cancers. Contrary to the initial hypothesis, it was found that MSI-High cancers were associated with higher FasL expression (p = 0.04) and a stronger intensity of FasL staining (p = 0.007). In addition, mucinous carcinomas were independently characterized by increased FasL expression (p = 0.03) and staining intensity (p = 0.0005). Higher FasL expression and staining intensity did not correlate with reduced TIL density or increased numbers of apoptotic TILs. However, consistent with the hypothesis that curtailment of the host anti-tumour immune response contributes to the poor prognosis in MSS cancers, it was found that apoptotic TILs were most abundant in MSS carcinomas and metastatic Dukes' stage C or D tumours (p = 0.004; p = 0.046 respectively). This study therefore suggests that MSS colorectal cancers are killing incoming TILs in an effective tumour counter-attack, but apparently not via membrane-bound FasL. Copyright (C) 2003 John Wiley Sons, Ltd.

Transposition of first digital pad for reconstruction of a palmar antebrachial soft tissue defect in a cat

An 8-year-old female neutered Siamese cat was presented with a recent history of incomplete excision of an apocrine gland adenocarcinoma from the palmar aspect of the right antebrachium, just proximal to the carpal joint. There was no evidence of metastasis. Wide surgical excision of the previous surgery site was performed resulting in a soft tissue defect. Partial reconstruction was achieved using digital pad transposition of the first digit (dewclaw), forming a local axial pattern flap that was transposed into the adjacent defect. The remaining defect was closed by primary apposition. The skin flap healed successfully. Some breakdown of the skin closed by primary apposition necessitated open wound management. The cosmetic and functional result of the first digital pad transposition was considered excellent, rendering it a useful means to reconstruct soft tissue defects in the carpal region.

Adenoma pleomórfico de septo nasal: relato de caso

As neoplasias nasais são bastante raras. Os tumores mais observados na cavidade nasal são papilomas epiteliais, angiomas, carcinoma de células transicionais, carcinoma pavimentoso e adenocarcinoma. O adenoma pleomórfico pertence ao grupo de tumores que aparecem com menor freqüência na fossa nasal, e é o tumor benigno glandular mais comum originado na cabeça e pescoço. A apresentação clínica típica dos pacientes com adenoma pleomórfico do septo nasal é de obstrução nasal unilateral, epistaxe e massa indolor na cavidade nasal. Em vista da raridade da apresentação clínica do adenoma pleomórfico nesta localização, os autores descrevem um caso de adenoma pleomórfico nasal em um paciente do sexo masculino, com 69 anos de idade, onde relatam os achados clínicos, critérios diagnósticos, tratamento, prognóstico e revisão da literatura.

Carcinoma apócrino na glândula parótida e na região submandibular

Os objetivos deste trabalho consistem na apresentação de um caso de carcinoma apócrino e na discussão de aspectos relacionados ao seu diagnóstico, tratamento e prognóstico. Os carcinomas com diferenciação apócrina que não correspondem aos casos de doença extramamária de Paget, de carcinoma ductal de mama, de adenocarcinoma das glândulas de Moll e de carcinoma ceruminal são tumores muito raros. Relatamos o caso de uma paciente do sexo feminino, negra, com 51 anos, na qual duas lesões de carcinoma apócrino acometeram a parótida esquerda (processo inicial e recidiva) e uma lesão envolveu a pele da região submandibular do mesmo lado. O exame histopatológico destas lesões mostrou a presença de neoplasia epitelial glandular infiltrativa com pleomorfismo celular e nuclear moderados; apresentando células poligonais ou arredondadas, com núcleos grandes e citoplasma eosinofílico e granular. Destacou-se a presença de secreção por decapitação apical na maior parte das células tumorais voltadas para a luz das estruturas císticas neoplásicas. Adicionalmente, foi encontrada a presença de focos de comedo-necrose e de material corado pelo PAS com e sem diastase. Apesar de não podermos definir com certeza qual a sede do tumor primário, com base nos aspectos histopatológicos compatíveis com o carcinoma apócrino cutâneo, consideramos que tenha sido, provavelmente, a lesão retirada da pele da região submandibular. A paciente foi submetida a tratamentos cirúrgicos e não apresentou alterações após um ano de acompanhamento, depois da retirada do tumor recidivante na parótida.

Metástases dos ossos gnáticos: estudo retrospectivo de 10 casos

Metástases em cavidade oral são extremamente raras, representando 1% de todas as neoplasias malignas orais. OBJETIVO: Analisar retrospectivamente a incidência de metástase nos maxilares, traçando seu perfil de comportamento epidemiológico. MATERIAL E MÉTODOS: Através de estudo retrospectivo, foram analisados o sexo, idade, localização topográfica da metástase, sítio do tumor primário e tipo histológico, no período de janeiro de 1980 a janeiro de 2000, de um total de 10 pacientes. RESULTADOS: Observou-se que 5 pacientes eram do sexo masculino (50%), 3 casos ocorreram nas 2ª e 4ª décadas de vida (30 e 30%). Concernente à localização topográfica da metástase, metade dos casos ocorreu na maxila e metade na mandíbula. A tireóide e próstata foram os sítios de tumor primário que mais metastizaram para os ossos gnáticos (3 casos cada) e o adenocarcinoma foi o tipo histológico de maior ocorrência de metástase (50%). Conclusões: As metástases nos maxilares acometem igualmente faixa etária, sexo e localização topográfica. A tireóide e próstata parecem ser os sítios mais freqüentes de metástase à distância, e o adenocarcinoma o tipo histológico de maior incidência de metástase.

Exposición ocupacional y cáncer de pulmón en fumadores

Las altas tasas de incidencia y mortalidad por cáncer de pulmón en hombres en Rosario, Argentina motivaron o estudio de 211 pacientes varones. Se comparon las edades al diagnóstico entre los tipos histológicos y ocupaciones, y edad de iniciación, duración e intensidad del hábito de fumar. La edad promedio al diagnóstico fue 61 años, sin diferencias por tipo histológico pero sí por hábito de fumar: 58 años los fumadores y 68 los ex-fumadores (p<0,0001). En estos pacientes se encontró un predominio de tumores epidermoides, lo que podria estar asociado a los contaminantes ocupacionales presentes en esta etapa de industrialización. La asociación entre tipo celular y ocupación fue altamente significativa (p<0,0001), encontrándose el adenocarcinoma con mayor frecuencia en administrativos (oficinistas, docentes, contadores, abogados) y el epidermoide en otras ocupaciones (agricultores, metalúrgicos), especialmente en quienes fueron primeramente agricultores y luego metalúrgicos.

PSA e medidas antropométricas em índios da Amazônia: avaliação da comunidade Parkatejê

OBJETIVO: O rastreamento com o PSA (antígeno prostático específico) para detecção precoce de câncer de próstata em uma comunidade nativa tem grande importância epidemiológica. Assim, realizou-se estudo com objetivo de verificar a ocorrência do câncer da próstata em uma tribo indígena da Amazônia e uma possível relação entre o aculturamento, a presença de sobrepeso (índice de massa corporal) e o aparecimento da doença. MÉTODOS: Foi realizado um levantamento dos hábitos e medidas antropométricas em 22 homens com idade presumida maior de 50 anos, de uma tribo isolada de 363 índios, autodenominados Parkatejê e Kikatêjê, vivendo na região Amazônica (Pará). Além dos exames físico e hematológicos, foram realizadas dosagens de PSA total e PSA livre. RESULTADO: Os níveis séricos de PSA total variaram de 0,35 a 25,8 ng/ml. Três nativos apresentaram PSA maior que 4,0 ng/ml e outros dois evidenciaram PSA entre 2,5 e 4,0 ng/ml. Biopsia prostática em dois nativos revelou a presença de adenocarcinoma de próstata em um e neoplasia intraepitelial em outro. Sobrepeso com índice de massa corporal >25 Kg/m² e relação cintura-quadril >0,9 foram observados em 68,1% e 72,7% do grupo estudado. CONCLUSÕES: Mudanças nutricionais decorrentes do contato com a civilização, como substituição da caça e fibras vegetais por alimentos mais calóricos, estão aumentando a freqüência de sobrepeso na comunidade indígena. Devido à associação entre incidência de câncer de próstata, dieta gordurosa e menor atividade física, pode-se presumir que o futuro testemunhará mais casos da neoplasia prostática, visto que vários de seus membros já evidenciaram altos níveis séricos de PSA.

Chemical and biological studies from an Azorean macroalga: Ulva rigida

3rd Portuguese Meeting on Medicinal Chemistry and 1st Portuguese-Spanish-Brazilian Meeting on Medicinal Chemistry, Aveiro, 28-30 Novembro 2012.