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Os mecanismos reguladores do ciclo celular e sua inter-relação com fatores de crescimento, oncogenes e anti-oncogenes têm se constituído nas áreas de maior avanço no estudo da biologia do câncer. Continuamente estão sendo descobertas novas proteínas envolvidas no complexo mecanismo que desencadeia as diferentes fases do ciclo celular, como também os seus mecanismos de ativação. A descoberta dessas proteínas e co-fatores que regulam as transições G1/S e G2/M e que atuam na replicação do material bem como o papel dos proto-oncogenes dentro do ciclo celular permitiu aumentar o conhecimento sobre as células ciclizantes como tarnbém, permitiu que estas pudessem ser detectadas mesmo sem a visualização de figuras mitóticas. O desenvolvimento de anticorpos monoclonais contra estas proteínas tornou viável o estudo, em larga escala, de taxas de proliferação celular em diferentes neoplaslas, uma vez que substâncias como Ki67, polimerase alfa e PCNA - Ciclina somente são expressas em células em proliferação. A detecção de células proliferativas permite, através de sua contagem, estimar as taxas do crescimento neoplásico com conseqüente repercussão no prognóstico da doença e na terapêutica do paciente. Neste artigo são revistos os mecanismos de controle do ciclo celular bem como os métodos de detecção de células proliferativas, enfatizando a aplicação de marcadores pela sua praticidade e confiabilidade.

Cancer is considered a genetic disease, being classified as an accumulative somatic disorder aside of the Mendelian diseases, the chromosomopaties and the multifactorial diseases. It has been demonstrated in several human cancers that specific mutations in some genes are related to hystopathologic features and tumor progression. Thereby, mutations represent potentially valuable markers in disease-stage detection and evaluation. Mutations associated with neoplasia development and evolution are very valuable, and the related genes are classified as: oncogenes, tumor suppressing genes, DNA repairing genes and cell cycle regulator genes. The factability to determine and characterize these genes and relate them with one or several steps of tumorogenesis, makes them molecular markers that let us predict risk, make an early diagnosis, confirm a diagnosis, establish prognosis, guide the therapy and determine resistance to treatments. Molecular methods used today for analysis of this markers offer great advantages: they are vary sensitive, use a small sample, are fast, can be easily automated, are easily interpreted, allows quantitations and, very importantly, they become cheaper when a large quantity of samples are handled. In this review we mention some types of cancers and molecular methods that can be used to take advantage of their biomarkers.

Twenty five percent of the medullary thyroid carcinoma (MTC) is hereditary and 5% is familiar (FMTC), or considered as multiple endocrine neoplasia (MEN) type 2A (17%) or 2B (3%). These diseases are the result of the autosomic dominant inheritance of a mutation in the RET protooncogene, in one out of 12 different known codons. We analyzed 7 families (2 MEN 2A and 5 FMTC). Six mutations were detected in the most frequent codon, 634 (2 MEN 2A y 4 FMTC) and one family with FMTC presented a novel mutation: a transition T > C at codon 630, resulting a C630A change. Among 57 individuals studied, 25 (43.85%) presented the mutation. Seven (28%) were asymptomatic carriers, including 5 children aged 11 +/- 3.2 years. The children underwent total thyroidectomy. The histopathologic examination showed C cells hyperplasia and microcarcinoma focus in both lobes, even in the presence of normal, basal or pentagastrine stimulated, calcitonine levels. In conclusion, we describe a germine novel mutation in the RET protooncogene: C630A; and the corresponding findings of C-cell disease in gene mutated carriers that emphasize the importance of prophylactic thyroidectomy as soon as the molecular diagnosis is confirmed.

Some types of malignant neoplasms are consequence of genetic changes. The starting of oncogenesis begins when some genetic alterations arises, or the genome acquires some peculiar and pathological traits owing to the action of physical, chemical or viral agents. These alterations set in motion an activatory phenomenon upon the proto-oncogene which is turned into an oncogene. The oncogene is responsible for fixed alterations of the genome inducing to an anomalous cellular growth. In squamous carcinomata of the head and neck has been observed mutations of the p-53 tumour-suppressor gene, alike amplifications of the ras-gene, of the C-myc proto-oncogene and also of the epidermal growth factor gene (EGFG). The viruses induce mutations on the genome. That would be the explanatory reason for the association carcinoma of the rhinopharynx-Epstein-Barr virus.

A series of 119 patients with 122 gastric carcinomas treated by gastrectomy, with a follow up of more than 5 years is presented. There were 80 (67.2%) men and 39 (32.8%) women with a mean age of 66.4 years. In 101 (84.9%) the diagnosis of cancer was endoscopic. Pain was the most frequent symptom (55.5%). Seventy two (59%) were localized in the antrum; 26 (21%) were cardial, and 24 (19.7%) were in the body. In 43.4% the size was smaller than 5 cm and in 56.6% it measured 5 cm or more. Eighty nine (73%) were of the intestinal type, 15 (12.3%) were diffuse and 18 (14.8%) were mixed. Eighty (65.6%) were low histological grade and 42 (34.4%) were high grade. Ten (9.2%) were early carcinomas and 112 (91.8%) advanced carcinomas. An amplification of the c-erbB-2 oncogene was associated with tumors that were smaller than 5 cm (p = 0.05) and with histological low grade (p = 0.005). A five years survival correlated with tumors smaller than 5 cm (p = 0.02), with parietal infiltration not surpassing the muscular layer (p = 0.001), and without lymph node metastases (p = 0.001). There was no association between survival and amplification of c-erbB-2 oncogene.

A brief review about the possible role of cell protooncogenes in embryonal development and neoplastic transformation is presented.