Integration of genomics in cancer care.

PURPOSE: The article aims to introduce nurses to how genetics-genomics is currently integrated into cancer care from prevention to treatment and influencing oncology nursing practice. ORGANIZING CONSTRUCT: An overview of genetics-genomics is described as it relates to cancer etiology, hereditary cancer syndromes, epigenetics factors, and management of care considerations. METHODS: Peer-reviewed literature and expert professional guidelines were reviewed to address concepts of genetics-genomics in cancer care. FINDINGS: Cancer is now known to be heterogeneous at the molecular level, with genetic and genomic factors underlying the etiology of all cancers. Understanding how these factors contribute to the development and treatment of both sporadic and hereditary cancers is important in cancer risk assessment, prevention, diagnosis, treatment, and long-term management and surveillance. CONCLUSIONS: Rapidly developing advances in genetics-genomics are changing all aspects of cancer care, with implications for nursing practice. CLINICAL RELEVANCE: Nurses can educate cancer patients and their families about genetic-genomic advances and advocate for use of evidence-based genetic-genomic practice guidelines to reduce cancer risk and improve outcomes in cancer management.

A novel SYBR-based duplex qPCR for the detection of gene dosage: detection of an APC large deletion in a familial adenomatous polyposis patient with an unusual phenotype.

BACKGROUND: Familial adenomatous polyposis (FAP) is a hereditary colorectal cancer syndrome caused by a loss of function of the APC gene. Large deletions in APC are a common cause of FAP; despite the existence of a variety of gene dosage detection methodologies, most are labor intensive and time and resource consuming. METHODS: We describe a new duplex qPCR method for gene dosage analysis based on the coamplification of a target and a reference gene in a SYBR Green reaction, followed by a comparison of the ratio between the target and the reference peaks of the melting curve for the test (patient) and control samples. The reliability of the described duplex qPCR was validated for several genes (APC, HPRT1, ATM, PTEN and BRCA1). RESULTS: Using this novel gene dosage method, we have identified an APC gene deletion in a FAP patient undergoing genetic testing. Comparative genomic hybridization based on microarrays (aCGH) was used to confirm and map the extent of the deletion, revealing a 5.2 MB rearrangement (5q21.3-q22.3) encompassing the entire APC and 19 additional genes. CONCLUSION: The novel assay accurately detected losses and gains of one copy of the target sequences, representing a reliable and flexible alternative to other gene dosage techniques. In addition, we described a FAP patient harboring a gross deletion at 5q21.3-q22.3 with an unusual phenotype of the absence of mental impairment and dysmorphic features.

Cluster of symptoms in women with breast cancer treated with curative intent.

PURPOSE: The purpose of this study is to verify that there is a cluster of symptoms in women with breast cancer who were treated with curative intent and are free of disease. METHODS: One hundred and thirty-eight patients were recruited from the Mastology Department of Hospital A.C. Camargo with breast cancer, who have been treated with curative intent and concluded adjuvant chemotherapy 3-24 months prior who may or may not be using hormone therapy. The characterization of the sample was made through descriptive statistics (mean, standard deviation, median, and percentage). For evaluation of the cluster of symptoms, the following were used: Pearson correlation coefficient among the scales of Profile of Mood States, EORTC-QLQ-C30, and EORTC-BR23 and a factor analysis with principal components analysis with promax rotation (oblique). For the extraction of factors, an eigenvalue of 1 was considered, and to evaluate the permanence of symptom factor, a load greater than 0.40 was considered. Statistical significance was defined as p value <0.05. RESULTS: Through factor analysis of data, three distinct groupings were observed. Factor 1 corresponds to the psychoemotional symptoms and grouped as depression, confusion, anger, tension, fatigue, and breast symptoms. Factor 2 corresponds to physical symptoms, which include pain, dyspnea, arm symptoms, and insomnia. Finally, factor 3 corresponds to gastrointestinal symptoms (inappetence, diarrhea, nausea, and vomiting). CONCLUSIONS: Through the data presented, the cluster of symptoms could be verified in women with breast cancer who were treated with curative intent and free of disease.

Clinical and Molecular Characterization of Brazilian Patients Suspected to Have Lynch Syndrome.

Lynch syndrome (LS) accounts for 3-5% of all colorectal cancers (CRC) and is inherited in an autosomal dominant fashion. This syndrome is characterized by early CRC onset, high incidence of tumors in the ascending colon, excess of synchronous/metachronous tumors and extra-colonic tumors. Nowadays, LS is regarded of patients who carry deleterious germline mutations in one of the five mismatch repair genes (MMR), mostly in MLH1 and MSH2, but also in MSH6, PMS1 and PMS2. To comprehensively characterize 116 Brazilian patients suspected for LS, we assessed the frequency of germline mutations in the three minor genes MSH6, PMS1 and PMS2 in 82 patients negative for point mutations in MLH1 and MSH2. We also assessed large genomic rearrangements by MLPA for detecting copy number variations (CNVs) in MLH1, MSH2 and MSH6 generating a broad characterization of MMR genes. The complete analysis of the five MMR genes revealed 45 carriers of pathogenic mutations, including 25 in MSH2, 15 in MLH1, four in MSH6 and one in PMS2. Eleven novel pathogenic mutations (6 in MSH2, 4 in MSH6 and one in PMS2), and 11 variants of unknown significance (VUS) were found. Mutations in the MLH1 and MSH2 genes represented 89% of all mutations (40/45), whereas the three MMR genes (MSH6, PMS1 and PMS2) accounted for 11% (5/45). We also investigated the MLH1 p.Leu676Pro VUS located in the PMS2 interaction domain and our results revealed that this variant displayed no defective function in terms of cellular location and heterodimer interaction. Additionally, we assessed the tumor phenotype of a subset of patients and also the frequency of CRC and extra-colonic tumors in 2,365 individuals of the 116 families, generating the first comprehensive portrait of the genetic and clinical aspects of patients suspected of LS in a Brazilian cohort.

Association of the p53 codon 72 polymorphism with clinicopathological characteristics of colorectal cancer through mRNA analysis.

TP53 represents a suitable candidate for a colorectal cancer susceptibility locus. The polymorphism in the p53 72nd codon involves a proline to arginine substitution, leading to changes in gene transcription activity, interaction with other proteins and modulation of apoptosis. Studies evaluating the association between this polymorphism and colorectal cancer (CRC) have shown inconsistent results, and none have evaluated the mRNA status of TP53. The aim of the present study was to evaluate the association between this SNP expression at the mRNA level in CRC samples and patient clinicopathological variables and prognosis, p53 protein expression and TP53 mutation. This is the first report to describe the mRNA expression of p53 codon 72 alleles in CRC. We evaluated 101 non-related patients with CRC treated at the A.C. Camargo Cancer Center in Brazil. RNA was isolated from frozen tumor tissues using a trizol-based protocol. The polymorphism was detected using RT-PCR followed by Sanger sequencing. Associations were analyzed using Pearson's Chi-square or Fisher's exact tests, logistic regression and Cox. This polymorphism was significantly associated with clinicopathological variables related to increased tumor aggressiveness. The expression of Arg72 (OR, 3.83; CI 1.02-14.35; P=0.046) and the TNM stage (OR, 7.15; CI 1.45-35.29; P=0.016) were found to be independent predictors for recurrence. These data suggest that the mRNA expression of the Pro72 allele is associated with less favorable tumor features. The allele frequency of the p53 Pro72 was 0.26. The analysis of mRNA is important to determine the specific contribution of the allele expressed. These results suggest that this polymorphism may play a role in CRC.

Mutational spectrum of the APC and MUTYH genes and genotype-phenotype correlations in Brazilian FAP, AFAP, and MAP patients.

BACKGROUND: Patients with multiple colorectal adenomas are currently screened for germline mutations in two genes, APC and MUTYH. APC-mutated patients present classic or attenuated familial adenomatous polyposis (FAP/AFAP), while patients carrying biallelic MUTYH mutations exhibit MUTYH-associated polyposis (MAP). The spectrum of mutations as well as the genotype-phenotype correlations in polyposis syndromes present clinical impact and can be population specific, making important to obtain genetic and clinical data from different populations. METHODS: DNA sequencing of the complete coding region of the APC and MUTYH genes was performed in 23 unrelated Brazilian polyposis patients. In addition, mutation-negative patients were screened for large genomic rearrangements by multiplex ligation-dependent probe amplification, array-comparative genomic hybridization, and duplex quantitative PCR. Biallelic MUTYH mutations were confirmed by allele-specific PCR. Clinical data of the index cases and their affected relatives were used to assess genotype-phenotype correlations. RESULTS: Pathogenic mutations were identified in 20 of the 23 probands (87%): 14 in the APC gene and six in the MUTYH gene; six of them (30%) were described for the first time in this series. Genotype-phenotype correlations revealed divergent results compared with those described in other studies, particularly regarding the extent of polyposis and the occurrence of desmoid tumors in families with mutations before codon 1444 (6/8 families with desmoid). CONCLUSIONS: This first comprehensive investigation of the APC and MUTYH mutation spectrum in Brazilian polyposis patients showed a high detection rate and identified novel pathogenic mutations. Notably, a significant number of APC-positive families were not consistent with the predicted genotype-phenotype correlations from other populations.

Evaluation of MLH1 I219V polymorphism in unrelated South American individuals suspected of having Lynch syndrome.

BACKGROUND: Some single-nucleotide polymorphisms are associated with higher risk of colorectal cancer development and are suggested to explain part of the genetic contribution to Lynch syndrome. AIM: To evaluate the mutL homolog 1 (MLH1) I219V polymorphism in 124 unrelated South American individuals suspected of having Lynch syndrome, based on frequency, association with pathogenic MLH1 and mutS homolog 2 (MSH2) mutation and clinical features. MATERIALS AND METHODS: DNA was obtained from peripheral blood and polymerase chain reaction (PCR) was performed, followed by direct sequencing. RESULTS: The Val allelic of the I219V polymorphism was found in 51.61% (64/124) of the individuals, with an allelic frequency of 0.3. MLH1 or MHS2 pathogenic mutations were found in 32.81% (21/64) and in 23.33% (14/60) of Val-carriers and non-carriers, respectively. CONCLUSION: The Val-carrying genotype was frequent in the studied population; however, it does not appear to exert any modifier effect on MLH1 or MSH2 pathogenic mutations and the development of colorectal cancer.

Ezrin expression as a prognostic marker in colorectal adenocarcinoma.

Ezrin protein acts in the regulation of cytoskeletal and directly influences survival and tumor progression; there is an increase in its expression in metastatic cells and tissues in several types of cancer including colorectal cancer. 250 Patients with colorectal cancer submitted to surgery from 1995 to 2002. Protein expression was carried through by Tissue Micro Array immunohistochemical tests of paraffined neoplasic tissues and associated with clinical variables. Differentiation degree, lymph node invasion, metastasis at diagnosis, and palliative surgery were associated to a higher expression of the protein and survival. Higher expression of the Ezrin correlates with tumor aggressiveness and worse prognosis for colorectal cancer.

Characterization of germline mutations of MLH1 and MSH2 in unrelated south American suspected Lynch syndrome individuals.

Lynch syndrome (LS) is an autosomal dominant syndrome that predisposes individuals to development of cancers early in life. These cancers are mainly the following: colorectal, endometrial, ovarian, small intestine, stomach and urinary tract cancers. LS is caused by germline mutations in DNA mismatch repair genes (MMR), mostly MLH1 and MSH2, which are responsible for more than 85% of known germline mutations. To search for germline mutations in MLH1 and MSH2 genes in 123 unrelated South American suspected LS patients (Bethesda or Amsterdam Criteria) DNA was obtained from peripheral blood, and PCR was performed followed by direct sequencing in both directions of all exons and intron-exon junctions regions of the MLH1 and MSH2 genes. MLH1 or MSH2 pathogenic mutations were found in 28.45% (34/123) of the individuals, where 25/57 (43.85%) fulfilled Amsterdam I, II and 9/66 (13.63%) the Bethesda criteria. The mutations found in both genes were as follows: nonsense (35.3%), frameshift (26.47%), splicing (23.52%), and missense (9%). Thirteen alterations (35.14%) were described for the first time. The data reported in this study add new information about MLH1 and MSH2 gene mutations and contribute to better characterize LS in Brazil, Uruguay and Argentina. The high rate of novel mutations demonstrates the importance of defining MLH1 and MSH2 mutations in distinct LS populations.

Neoadjuvant chemoradiation therapy for soft tissue sarcomas of the extremities.

INTRODUCTION AND OBJECTIVE: Neoadjuvant and adjuvant therapies for soft tissue sarcomas of the extremities are still controversial. The aim of this study was to analyze the results of a protocol of neoadjuvant chemoradiation therapy for extremity sarcomas. METHODS: A retrospective analysis was carried out in a consecutive series of 49 adult patients with advanced extremity soft tissue sarcomas that could not be resected with adequate margins during the primary resection. All patients were treated with a protocol of preoperative radiation therapy at a total dose of 30 Gy, concomitant with doxorubicin (60 mg/m(2)) chemotherapy. The main endpoints assessed were local recurrence-free survival, metastasis-free survival and overall survival. The median follow-up time was 32.1 months. RESULTS: The five-year local recurrence-free survival, metastasis-free survival and overall survival rates were 81.5%, 46.7% and 58.3%, respectively. For high-grade tumors, the five-year metastasis-free and overall survival rates were only 36.3% and 41.2%, respectively. Severe wound complications were observed in 41.8% of the patients who underwent surgery. These complications precluded adjuvant chemotherapy in 73.7% (14/19) of the patients eligible to receive it. CONCLUSIONS: In this study, neoadjuvant chemoradiation therapy was associated with a good local control rate, but the distant relapse-free rate and overall survival rate were still poor. The high rate of wound complications modified the planning of adjuvant treatment in most patients.

Atuação do enfermeiro em oncologia na perspectiva da genética e genômica / Oncology nursing practice from the perspective of genetics and genomics / Práctica de lo enfermero en oncología en la perspectiva de la genética y genómica

Este artigo tem como objetivo refletir sobre a atuação do enfermeiro em oncologia, sob a perspectiva da genética e da genômica, e sobre seu papel como membro integrante da equipe multiprofissional e interdisciplinar de aconselhamento genético oncológico. Trata-se de uma reflexão, fruto de leitura minuciosa da literatura da área, acrescida da experiência dos autores e discussões em grupo de pesquisa. No transcorrer desse trabalho, foi possível constatar que o enfermeiro precisa considerar o cuidado de saúde baseado em genômica e apropriar-se de competências essenciais. Essas competências abrangem a habilidade de mobilizar recursos genômicos na coleta da história familiar e nas orientações sobre testes genéticos a famílias em risco para síndromes neoplásicas hereditárias. O profissional de enfermagem pode atuar como referência para os demais membros da equipe de saúde, com potencial para integrar seus conhecimentos no cuidado, no ensino e em pesquisas em oncologia, sob a ótica da genética e da genômica.

This study aimed to reflect on oncology nurses' practice from the perspective of genetics and genomics, and their role as a member of the multiprofessional and interdisciplinary cancer genetics counseling team. This reflection is a result of the detailed reading of literature in the area, increased by the authors' experience and research group discussions. In the course of this work, it was verified that the nurse needs to consider genomic-based health care and incorporates essential competencies. These competencies include the ability to mobilize genomic resources in the family history assessment and in the guidelines on genetic testing for families at risk for hereditary neoplastic syndromes. The nursing staff may act as a reference for other members of the health team, with the potential to integrate their knowledge on care, teaching and research in oncology from the viewpoint of genetics and genomics.

Este estudio objetivó reflexionar sobre la práctica del enfermero en oncología en la perspectiva de la genética y genómica, y su papel como miembro del equipo multiprofesional e interdisciplinario del asesoriamento genético oncológico. Esta reflexión es resultado de lectura atenta de la literatura, además de la experiencia de los autores y discusiones del grupo de investigación. En el curso de este trabajo, fue posible constatar que el enfermero debe tener en cuenta el cuidado de salud basado en genómica y se apropiar de competencias esenciales. Estas competencias incluyen habilidad de movilizar recursos genómicos en la colecta de la historia familiar y orientaciones sobre testes genéticos para familias en riesgo de síndromes neoplásicas hereditarias. El profesional de enfermería puede actuar como referencia para los demás miembros del equipo de salud, con posibilidad de integrar sus conocimientos en asistencia, enseñanza e investigación en oncología, desde el punto de vista de la genética y genómica.

Predictors of quality of life in colorectal cancer patients treated with curative intention

This study aims to evaluate predictors of quality of life in patients treated for colorectal cancer (CRC) with curative intention. PATIENT/METHODS: All patients with CRC treated with curative intention were interviewed by telephone using the SF-36 questionnaire.RESULTS/FINDINGS: One hundred and one patients (44 men, 57 women) were included in this study with a mean age of 60.8 years. Sixty-nine patients were treated for rectal cancer and 32 for colon cancer. Of the total, 23 patients had a stoma (22.8%) and 55 (54.5%) reported comorbidities. The means of the SF-36 scales varied between 90 (emotional aspects) and 65 (physical aspects). Presence of comorbidities was a predictor factor of quality of life in six of eight SF-36 scales. The female patients attained lower scores on three scales: functional capacity, pain and vitality. Patients age 60 or over attained lower scores on two SF-36 scales: functional capacity and social aspects. Patients with a stoma had lower score on limitation due to emotional aspects. We concluded that comorbidities affect the quality of life of individuals with colorectal cancer. Health professionals should be prepared to address not only the limitations caused by cancer and its treatment, but also the limitations caused by chronic diseases.

Associação entre o nível de atividade física e os estados de humor entre pacientes com câncer de mama tratadas com intuito de cura / The association between the level of physical activity and mood states in patients with breast cancer treated with curative intent

Objetivo: Analisar a associação entre o nível de atividade física e os estados de humor entre pacientes com câncer de mama tratadas com intuito de cura. Metodologia: Foram entrevistadas 354 mulheres que cumpriram os critérios de inclusão e exclusão e assinaram o termo de consentimento livre esclarecido. Para análise dos estados de humor foi utilizado o Profile Of Mood States - POMS. Para mensuração do nível de atividade física utilizou-se o Baecke. A caracterização da amostra se baseou na estatística descritiva (média, desvio padrão, mediana e porcentagem).O nível de atividade física, segundo o escore do Baecke, foi categorizado em tercis e foi considerado como a variável independente. Foi realizado o teste de médias com as escalas POMS. Para a associação entre o nível de atividade física através do escore Baecke e das escalas do POMS, foi realizado o teste t e ANOVA para teste de médias. Para todos os testes foi estabelecido um erro a = 5%, ou seja, os resultados foram considerados estatisticamente significativos quando p < 0,05. Resultados: Quando se comparou a média na pontuação do POMS de acordo com a atividade física do Baecke dividido em tercis, verificou-se associação entre a atividade física com Vigor (p<0,001) e a Fadiga (p=0,019). Conclusão: Conclui-se que a atividade física é um fator relacionado com a melhora nos estados de humor nas mulheres com câncer de mama tratadas com intenção curativa.

Neoadjuvant chemoradiation therapy for soft tissue sarcomas of the extremities

INTRODUCTION AND OBJECTIVE: Neoadjuvant and adjuvant therapies for soft tissue sarcomas of the extremities are still controversial. The aim of this study was to analyze the results of a protocol of neoadjuvant chemoradiation therapy for extremity sarcomas. METHODS: A retrospective analysis was carried out in a consecutive series of 49 adult patients with advanced extremity soft tissue sarcomas that could not be resected with adequate margins during the primary resection. All patients were treated with a protocol of preoperative radiation therapy at a total dose of 30 Gy, concomitant with doxorubicin (60 mg/m²) chemotherapy. The main endpoints assessed were local recurrence-free survival, metastasis-free survival and overall survival. The median follow-up time was 32.1 months. RESULTS: The five-year local recurrence-free survival, metastasis-free survival and overall survival rates were 81.5 percent, 46.7 percent and 58.3 percent, respectively. For high-grade tumors, the five-year metastasis-free and overall survival rates were only 36.3 percent and 41.2 percent, respectively. Severe wound complications were observed in 41.8 percent of the patients who underwent surgery. These complications precluded adjuvant chemotherapy in 73.7 percent (14/19) of the patients eligible to receive it. CONCLUSIONS: In this study, neoadjuvant chemoradiation therapy was associated with a good local control rate, but the distant relapse-free rate and overall survival rate were still poor. The high rate of wound complications modified the planning of adjuvant treatment in most patients.

Familial adenomatous polyposis: data from the Hereditary Colorectal Cancer Registry (HCCR)

Family adenomatous polyposis (FAP) is a dominant autossomic disease responsible for nearly 1% of colorectal cancer (CRC) cases caused by mutations in gene APC and nearly complete penetrance. The identification of germinative mutations can be useful in the definition of the therapeutic conduct by means of the correlation genotype-phenotype. Objective: To describe clinical and molecular characteristics of families with FAP or attenuated FAP. Method: The study included families registered in the Hereditary Colorectal Cancer Registry of A.C.Camargo Hospital. Cancer records were registered and heredograms were created. Data were collected and stored in a database. Results: From 1992 to 2007 22 families were registered that had FAP, 16 with classic FAP, nine with Gardner Syndrome, and 6 with attenuated FAP. From 604 individuals, 120 had polyposis, 62 CRC, 10 desmoid tumors, three breast tumors, two tumors of the stomach, two thyroid tumors and one with prostate tumor. From 22 families, three were submitted to molecular analysis and mutations were identified in gene APC. Discussion: Half of the individuals presented CRC concomitant to polyposis, which can indicate a late diagnostic of the disease; three identified mutations presented correlations genotype-phenotype as predicted by the literature. Follow-up of patients with FAP, although they account for less than 1% of CRC cases, is vital for early cancer diagnosis.

Frequency of Colorectal Cancer and Extracolonic Tumors in Families That Meet Amsterdam Criteria I and II: Results From Hospital A. C. Camargo Hereditary Colorectal Cancer Registry

An estimated 1% to 10% of all colorectal tumors (CRC) are related to high-penetrance genes. Families with Lynch Syndrome, caused by mutations in MMR repair genes, present a high frequency, not only of CRC, but also extracolonic tumors. Objective:To verify the frequency of CRC and extracolonic cancers in families that meet Amsterdam I and II criteria. Methods: Families had been included that meet Amsterdam I and II criteria, in the Registry of Colorectal Cancer of A. C. Camargo Hospital from 1992 to 2007. Family history was taken and stored in the Cyrillic® 2.1 software. Data collection forms were filled. Results:1578 individuals were identified, and 337 of them presented tumors. CRC was the most frequent, with 221 individuals,with a mean age of 46 years at diagnosis. The most frequent extracolonic tumors were breast (17 cases), endometrium (15), stomach (14), urinary (12), leukemia (9), and prostate (6). Discussion: As expected, the age at diagnosis of colorectalcancer was younger than the general population; breast tumor was the most frequent; molecular studies must differentiate patients with Lynch Syndrome (LS) from those with familial colorectal cancer.

P16 and p27 Immunohistochemical Expression in Colorectal Cancer: Analysis of 128 Patients

P16 and p27 are inhibiting proteins of cyclin-dependent kinases (CDKIs) that act in the restriction points of the cellular cycle, and it avoids its progression to DNA verification and repair by the cellular apparatus. This way, there should be, physiologically, an inverse relation between the expression of these proteins and cellular proliferation. However, what is really observed are changeable amounts of p27 in normal and tumor tissues. P16 participation in tumorigenesis is controversial. The expression of p16 and p27 as a prognostic factor in colorectal cancer (CRC) patients is controversial. Objetive: To establish a correlation between p16 and p27 immunohistochemical expressions with clinical and anatomopathological variable from patients with CRC. Material and methods: descriptive and retrospective study, with 128 CRC patients, treated surgically between 2000 and 2004, with available material for immunohistochemical analysis through standardized methods. The association between categorical variables was done using Chi-square, Pearson or Fisher?s Exact tests, and the continuous variables were analyzed by t-Student. Global survival and disease-free period were calculated according to Kaplan-Meier method and the associations through log-rank test. Results: The average follow-up time of patients was 35 months. Positivity of p16 was detected in 100% of cases. Negativity of p27 in 6.3% (n=8) of cases, with a significant association (p30.05) between p27 negative and tumors located in right colon (62.5%, n=5) and mucinous (62.5%, n=5). The average global survival was 54.8 months, and the significant clinical and pathological variables associated to survival were: better for curative surgeries; better for early stages; better for well-differentiated tumors; worse for cases with sanguineous or vascular lymphatic invasion; worse for perineural invasion. Conclusions: p27 negative is more frequent in right colon...

p53 and p21 Immunohistochemistry in Colorectal Cancer: Clinical and Pathological Correlation in 128 Cases

Mutations of tumoral suppressor TP53 gene are present in 75% of colorectal cancer (CRC) cases. Immunohistochemistry isa method capable of demonstrating the abnormal accumulation of p53 protein in the cell. Some studies associate p53immunohistochemical positivity and a worse prognosis, while others do not confirm this finding. There are controversiesregarding the prognostic value of p53 in CRC. The same doubts apply to p21 protein, activated by p53, which is the mainresponsible for stopping the cell cycle (checkpoints), both for repair or apoptosis purposes. Objective: The objective of thisstudy is to correlate p53 and p21 immunohistochemical expression both with clinical and anatomopathological variables andwith survival rates of patients with CRC. Materials and Methods: This is a descriptive and retrospective study having asresearch subjects 128 patients affected by CRC and treated surgically from 2000 to 2004, with available surgical specimensfor immunohistochemical analysis using standardized methods. The association among categorical variables was done byPearson chi-square or Fisher exact tests, and the continuous variables were analyzed by t-Student test. Overall survival anddisease-free period rates had been calculated according to Kaplan-Meier method and the associations by log-rank test. Results:Follow-up average time was 35 months. p53 and p21 alterations had been detected, respectively, in 67.2% and 27. 3% ofcases, with a significant association (p<0.05) between p53 and tumors located in rectum (76.0%) and left colon (70.7%), andbetween p21 and right colon (43.2%). p21 positive expression was related to CRC diagnostic at an older median age. Overallsurvival was 54 months, and the significant clinical and pathological related variables were the following: better for curativesurgeries; better for precocious stages; better for well-differentiated tumors; worse for cases with sanguineous or lymphatic...

Number of Disected Lymph Nodes In Colorectal Cancer Patients SubmittedTo Radical Surgery: The Quality of Oncology Treatment

Introduction: the correct evaluation of lymph node disease influences the therapeutical decisions of colon and rectal cancer(CRC) patients. The number of dissected lymph nodes is a variable that have prognostic value and serves as an indicator of thequality of oncology treatment. For a correct evaluation of N stage to be accepted, the minimum number of dissected lymphnodes considered must be 12. In rectal cancer patients submitted to neoadjuvant radiochemotherapy, the interpretation of thenumber of dissected lymph nodes remains inconclusive. Objective: is to evaluate the number of dissected lymph nodes in CRCpatients submitted to curative surgery and determine this latter impact in oncologic treatment results. In cases of rectalcancer, to study the effect of neoadjuvant radiochemotherapy in dissected lymph nodes count. Method: in the period 1991-2004, 852 CRC patients were treated in Hospital A. C. Camargo . Patients with metastases at the time of diagnosis,synchronous and metachronic tumors, total colectomy or total proctocolectomy and hereditary colorectal cancer were excluded.The sample was constituted by 423 patients with sporadic colorectal adenocarcinoma who undergone curative radical surgery(168 colon primary tumors and 255 rectal tumors). Colon cancer patients, treated primarily by surgery, had also receivedadjuvant chemotherapy (5-FU) according to risk criteria. Rectal cancer patients with fixed or half-fixed injuries or clinicallycompromised lymph nodes (T3, T4 or N+) had received neoadjuvant radiochemotherapy, followed by surgery and chemotherapy(5-FU). Results: the median of the number of dissected lymph nodes in colon cancer patients was 17. In the case of rectalcancer patients, the median of dissected lymph nodes in the groups with and without neoadjuvant radiochemotherapy had beenrespectively 9 and 15 (p<0.001). 5-year specific survival rates for colon and rectal cancer patients were respectively...