Pharmaco-Geno-Proteo-Metabolomics and Translational Research in Cancer.

The diagnosis, prognosis and treatment of cancer has had a great improvement due to the "omics" technologies such as genomics, proteomics, epigenomics, pharmacogenomics, and metabolomics. The technological progress of these technologies has allowed precision medicine to become a clinical reality. The study of different biomolecules such as DNA, RNA and proteins has helped to detect alterations in genes, changes in gene expression profiles and loss or gain of protein function, which allows us to make associations and better understand the cancer biology. Data obtained from different "omics" technologies gives a complementary spectrum of information that helps us to understand and unveil new information for a better diagnosis, prognosis, prediction of new molecular targets of anticancer therapies, etc. This chapter presents a general landscape of the interaction between the Pharmaco-Geno-Proteo-Metabolomic and translational medicine research in cancer.

Frequency of BRAF V600E Mutation in the Mexican Population of Patients With Metastatic Melanoma.

PURPOSE: The BRAF V600E mutation has been described in melanomas occurring in the Caucasian, European, and Asian populations. However, in the Mexican population, the status and clinical significance of BRAF mutation has not been researched on a large scale. METHODS: Consecutive BRAF-tested Mexican patients with metastatic melanoma (n = 127) were analyzed for mutations in exon 15 of the BRAF gene in genomic DNA by real-time polymerase chain reaction technology for amplification and detection. The results were correlated with the clinical-pathologic features and the prognosis of the patients. RESULTS: The frequency of somatic mutation V600E within the BRAF gene was 54.6% (43 of 127 patients). Nodular melanoma was the most prevalent subtype in our population, with BRAF mutations in 37.2% (16 of 55 patients). In contrast, superficial spread had a frequency of 18.6% BRAF mutation (eight of 24). Other clinicopathologic features were assessed to correlate with the mutation status. CONCLUSION: This study searched for the most prevalent BRAF V600E mutation type in melanoma in a heterogeneous population from Mexico. Nodular melanoma was found to be the most prevalent in metastatic presentation and the presence of BRAF V600E mutation, perhaps related to the mixed ancestry; in the north, ancestry is predominantly European and in the south, it is predominantly Asian. The outcomes of the mutation correlations were similar to those found in other populations.

Atypical small acinar proliferation: utility of additional sections and immunohistochemical analysis of prostatic needle biopsies.

BACKGROUND: In surgical pathology, atypical small acinar proliferation is commonly detected in prostate biopsies. Most studies on atypical small acinar proliferation have examined morphological characteristics and the utility of immunohistochemical studies. However, these resources are not available to many pathology departments. We have found that examining additional sections is a simple and inexpensive method that allows better evaluation of focal prostatic glandular atypia. OBJECTIVES: The present report compares the diagnostic utility of immunohistochemical techniques versus examining additional sections in prostate biopsies with focal glandular atypia. PATIENTS AND METHODS: Thirty recently studied prostate biopsies with focal glandular atypia were selected. In each case, 3 additional levels were examined. An immunohistochemical study was performed on one level using an antibody against high-molecular-weight keratin (34BetaE12). Two additional sections were stained with hematoxylin and eosin. RESULTS: The diagnosis of focal carcinoma was established with only additional sections in 4 cases (13.3%). In 2 of these biopsies, additional areas of carcinoma were found that were not identified in the original sections. In 4 other cases, immunohistochemical analysis was the only useful method for diagnosing cancer. In 9 cases (30%), both methods were useful for classifying focal glandular atypia as carcinoma. In the remaining 13 cases,neither immunohistochemical analysis nor additional sections were useful in changing the diagnosis of focal glandular atypia. CONCLUSIONS: Focal glandular atypia in prostatic needle biopsies should be routinely examined with additional sections, particularly when immunohistochemical analysis is not possible. Some biopsies with atypical glandular proliferation may show focal carcinoma in additional sections, even if the immunohistochemical analysis did not provide a diagnosis of malignancy. Additional sections can also reveal areas of carcinoma that were not apparent in the original sections.

[Trends of thyroid pathology in a referral center: steady prevalence of papillary thyroid carcinoma but goiter increase in thyroidectomies]. / Tendencias en patología tiroidea en un centro de referencia: prevalencia estable del carcinoma papilar e incremento de hiperplasia nodular en tiroidectomías.

INTRODUCTION: Changes in the prevalence of papillary thyroid carcinoma (PTC) have been reported in institutions and national cancer registries. OBJECTIVE: To describe time trends in benign and malignant thyroid diseases in a national endocrine referral center. MATERIALS AND METHODS: Systematic review and classification of consecutive specimens with slides/paraffin blocks in surgical pathology archives (January 1990 to December 2009). Institutional registries, size, type of surgery and number of inclusion blocks were recorded. Patients whose registries were granted before January 1990 without nodules, but treated after twelve months for a suspicious thyroid lesion, were included. These patients in a passive follow-up permitted incidence density calculations. Cases were grouped by quinquennium. RESULTS: Institutional registers were conceded to 103,961 persons worthy of attention, and 1,269 were submitted to thyroidectomies (1.2%). One hundred twenty four patients none treated for thyroid diseases before 1990, developed thyroid nodules after 1991. The incidence density for goiter was 0.05 person/year and for PTC 0.04 person/year in that group. In all series woman to man relation was 9:1 with a mean age of 45 years. Total or near total thyroidectomies were performed in 60% patients and benign diseases were diagnosed in 732 (52%) cases. Thyroid surgeries increased since 2005 (p=0.03) with a rise in goiter prevalence (0.25, 0.31, 0.35, 0.38, p for trend 0.0005), without significant increase in PTC prevalence (0.41, 0.43, 0.35, 0.40, p for trend 0.71) in thyroidectomies. CONCLUSIONS: Goiter as the only finding in thyroid specimens increased 52% in the last 20 years. PTC prevalence is steady with a higher number of tumors<3 cm.

Cribriform carcinoma of the gallbladder: a clinicopathologic study of 7 cases.

Carcinomas of the gallbladder are morphologically heterogeneous. Some are similar or mimic carcinomas that commonly arise in other organs and therefore can be confused with metastatic lesions. We report here the clinicopathologic features of 7 cribriform carcinomas of the gallbladder that resemble cribriform carcinomas of the breast. Five patients were women and 2 men whose ages ranged from 31 to 72 years (average age 57 y). These 7 patients were younger than those with conventional adenocarcinomas of the gallbladder (average age for males 71 y and average age for females 72 y). Five patients had cholelithiasis. The youngest patient, a 31-year-old woman, had no gallstones. Instead, she had an osteosarcoma removed from her distal femur, 4 years before. Although the osteosarcoma in this patient may be coincidental, a true association could not be entirely excluded. None of the 4 cribriform carcinomas of the gallbladder tested showed immunoreactivity for estrogen and progesterone receptors. Three patients with high nuclear grade cribriform carcinomas died as a result of the tumor which infiltrated the liver by direct extension; 3 patients with low nuclear grade cribriform carcinomas confined to the gallbladder wall survived 4 to 7 years after cholecystectomy and 1 patient was lost to follow-up. In conclusion, this study provides support to previous observations that a small proportion of gallbladder carcinomas display an unusual but predominant cribriform pattern similar to that of some invasive breast carcinomas. In contrast to mammary cribriform carcinomas, those arising in the gallbladder occur in individuals usually with gallstones, may coexist with skeletal osteosarcoma, lack estrogen and progesterone receptors, and behave aggressively like conventional adenocarcinomas of the gallbladder.