Organization of a tumor bank: the experience of the National Cancer Institute of Mexico.

A tumor bank (TB) is an ordered collection of neoplastic samples, normal tissue, and/or fluids preserved under optimal conditions, as well as storing patients' clinical information. The objective of this article is to outline the planning and logistics necessary for the functioning of the Instituto Nacional de Cancerología (INCan) TB in Mexico City. For the planning and logistics of a TB, several technical, legal, medical, structural, and physical aspects were considered, which can be grouped under four headings: (1) design and structure, (2) equipping the area and informatics, (3) ethical-legal aspects, and (4) sample collection, preservation, and quality control. One crucial element of interinstitutional interest will be the transfer of these concepts to the different oncological centers, integrating in this manner a network that enables the exploration of the different pathologies from therapeutic, epidemiological, and molecular points of view.

Mortality due to lung cancer in Mexico.

The highest mortality due to cancer worldwide for both genders corresponds to lung cancer (1,179,000 deaths). In Mexico, the crude mortality rate due to lung cancer was of 5.01 per 10(5) inhabitants in 1979. The most important risk factor is smoking. The present study was aimed at analyzing the mortality due to lung cancer in Mexico, assessing data from each of the states constituting the Mexican Republic during the 1998-2004 period. Data were obtained from the National Institute of Statistics, Geography and Informatics (INEGI, for its initials in Spanish) corresponding to deaths due to lung cancer (1998-2004). We estimated the mean annual mortality rate (MAMR) for each of the 32 states of Mexico. We used the "World Population Standard". The MAMR was standardized according to age (ARS) direct method, and the standard error was determined by Poisson's approximation at a 95% confidence interval. To know the excess risk due to mortality, we calculated the standardized mortality ratios (SMRs) of ARS for each federal state, using the national rate as reference. In this period, 397,400 deaths due to malignant neoplasms were recorded, corresponding 45,578 (11.5%) to lung cancer; for men, 31,025 (68.1%) with MAMR of 8.9 and the respective ARS of 13.2 both x10(5) inhabitants. For women, results were 4553 (31.9%) deaths with MAMR of 4.1 and ARS of 5.4 both x10(5) inhabitants. The highest mortality rates due to lung cancer in both genders were observed in the north of Mexico, whereas for women this was observed in the central states. Although smoking is the main risk for lung cancer, there are other factors such as environmental pollution or exposure to toxicants that could be associated to this cancer. The years potentially lost due to lung cancer were 258,550 for men and 133,315 for women, with a total of 391,865 according to histopathology registry neoplasm malignant RHNM (1985-1995). Studies focused on the characterization and measurement of polluting agents would be a good start to determine the level of participation of air pollution in the development of lung cancer.

Breast malignant phyllodes tumour metastasising to soft tissues of oral cavity.

Metastases from infraclavicular neoplasms to the oral cavity are rare, and the anatomical structures most frequently affected are the maxillae. The primary sites that develop metastases to head and neck include lung, breast, liver, thyroid gland, kidney and melanomas, among others. The breast is one of the usual primary regions that can present them. In the literature, most metastases to these regions correspond to squamous cell carcinomas and adenocarcinomas; few studies report other type of neoplasms such as phyllodes tumour (PT) that present this behaviour. The importance of identifying metastatic disease to the oral cavity, be it as the first manifestation of a neoplasm from unknown origin or as a development in the course of the disease, is that it allows determination of adequate treatment, which has an effect on the patient's prognosis. The usual behaviour of PT is frequent recurrence and, when metastases are present, these are to lungs and bone. Two cases of malignant PT metastasising to tongue and lip are presented, as well as a review of the literature.

Braf V600E mutation in melanoma: translational current scenario.

Melanoma was one of the translational cancer examples in clinic, including target therapy related to specific biomarkers impacting in the outcome of melanoma patients. Melanomagenesis involved a wide variety of mutations during his evolution; many of these mutated proteins have a kinase activity. One of the most cited proteins in melanoma is BRAF (about 50-60 % of melanomas harbors activating BRAF mutations), for these the most common is a substitution of valine to glutamic acid at codon 600 (p.V600E). Therefore, the precise identification of this underlying somatic mutation is essential; knowing the translational implications has opened a wide view of melanoma biology and therapy.

Comparing the effects of endogenous and synthetic cannabinoid receptor agonists on survival of gastric cancer cells.

AIMS: Anti-neoplastic activity induced by cannabinoids has been extensively documented for a number of cancer cell types; however, this topic has been explored in gastric cancer cells only in a limited number of approaches. Thus, the need of integrative and comparative studies still persists. MATERIALS AND METHODS: In this study we tested and compared the effects of three different cannabinoid receptor agonists-anandamide (AEA), (R)-(+)-methanandamide (Meth-AEA) and CP 55,940 (CP)- on gastric cancer cell morphology, viability and death events in order to provide new insights to the use of these agents for therapeutic purposes. KEY FINDINGS: The three agents tested exhibited similar concentration-dependent effects in the induction of changes in cell morphology and cell loss, as well as in the decrease of cell viability and DNA laddering in the human gastric adenocarcinoma cell line (AGS). Differences among the cannabinoids tested were mostly observed in the density of cells found in early and late apoptosis and necrosis, favoring AEA and CP as the more effective inducers of apoptotic mechanisms, and Meth-AEA as a more effective inducer of necrosis through transient and rapid apoptosis. SIGNIFICANCE: Through a comparative approach, our results support and confirm the therapeutic potential that cannabinoid receptor agonists exert in gastric cancer cells and open possibilities to use cannabinoids as part of a new gastric cancer therapy.

Clinicopathological characterization of primary oral and sinonasal melanoma in a referral centre in Mexico City: 2000-2012.

In Mexico, there have been few studies on primary oral and sinonasal melanoma, an aggressive neoplasm with a low survival rate and few therapeutic alternatives. Further, there is limited information about its clinical and histopathological characteristics. The aim of this retrospective study was to describe the clinicopathological profile of these tumours in patients attending a major oncology reference centre in Mexico City over a 12-year period. Demographic and clinical data were obtained from the clinical charts, and histopathological features were evaluated. χ(2), Fisher's exact, and Mann-Whitney U-tests were used for analysis; significance was set at P<0.05. Thirty-three cases were studied (73% sinonasal melanoma (SNM) and 27% oral melanoma (OM)); 58% were female and the median age was 66 (Q1-Q3 55.5-75) years. Compared with OM patients, SNM patients had a shorter time to diagnosis (16.7 vs. 11.7 months, P=0.022), were identified at earlier stages (33.3% vs. 58.3%, P=0.010), and all presented symptoms (66.7% vs. 100%, P=0.015). All samples showed vertical growth and 96.9% exhibited pleomorphism. A higher proportion of cases with pleomorphism developed metastases at follow-up than those without (60% vs. 12.5%, P=0.026). The present study provides valuable information that could form the basis of future studies in the search for advanced therapy modalities.

On the effects of CP 55-940 and other cannabinoid receptor agonists in C6 and U373 cell lines.

Cannabinoid receptor (CBs) agonists affect the growth of tumor cells via activation of deadly cascades. The spectrum of action of these agents and the precise role of the endocannabinoid system (ECS) on oncogenic processes remain elusive. Herein we compared the effects of synthetic (CP 55-940 and WIN 55,212-2) and endogenous (anandamide or AEA) CBs agonists (10-20 µM) on morphological changes, cell viability, and induction of apoptosis in primary astrocytes and in two glioblastoma cell lines (C6 and U373 cells) in order to characterize their possible differential actions on brain tumor cells. None of the CBs agonist tested induced changes in cell viability or morphology in primary astrocytes. In contrast, CP 55-940 significantly decreased cell viability in C6 and U373 cells at 5 days of treatment, whereas AEA and WIN 55,212-2 moderately decreased cell viability in both cell lines. Treatment of U373 and C6 for 3 and 5 days with AEA or WIN 55,212-2 produced discrete morphological changes in cell bodies, whereas the exposure to CP 55-940 induced soma degradation. CP 55-940 also induced apoptosis in both C6 and U373 cell lines. Our results support a more effective action of CP 55-940 to produce cell death of both cell lines through apoptotic mechanisms. Comparative aspects between cannabinoids with different profiles are necessary for the design of potential treatments against glial tumors.

Epithelioid sarcoma of penis.

A case of epithelioid sarcoma of the penis in a thirty-two-year-old man is presented. It had been present for two and one-half years as a small nodule on the ventral aspect at the base of the penis that eventually grew to large dimensions causing pain and extreme dysuria. A local resection was done; however, when tumor recurred, penectomy was undertaken followed by an incomplete course of radiotherapy. Fifteen months after surgery the patient was free of local recurrence but was in poor condition with metastases to regional and distant lymph nodes, lungs, and scalp--a pattern of spread characteristic of these tumors. This is a typical example of epithelioid sarcoma clinically, histologically, and ultrastructurally, despite the rare location.

Malignant melanoma of the oral cavity: diagnosis and treatment experience in a Mexican population.

Oral malignant melanoma is uncommon, accounting for 1-8% of all malignant melanomas. All previous papers have reported small numbers of cases or have retrospectively reviewed case reports from the literature. The following case reports concern malignant melanoma of the oral cavity seen at the Instituto Nacional de Cancerología, Mexico City, during the period of 1982-96. Demographic, clinical and histopathological data were collected. Our 15 patients consisted of 6 males and 9 females. The mean age was 52.6 years (range: 35 to 80 years). The hard palate was the most common area affected with 11 cases (73%). At the time of the initial examination, a pigmented mass was apparent in 100% of the patients. All our surgical cases were treated with wide resection; 8 patients received adjuvant radiation, 4 were treated with surgery alone and 1 case received radiation and chemotherapy before the surgery. Local control of the primary lesion was possible in 14 of the 15 cases. Some patients received therapeutic or elective lymph node dissection. The median survival was 16.9 months (mean: 12.5 months). The 2- and 5-year survival rates were 26.6 and 6.6%, respectively.

Well-differentiated intraosseous osteosarcoma of the jaws: experience of two cases from the Instituto Nacional de Cancerología, México.

Osteosarcomas of the jaws represent less than 10% of all osteosarcomas, and most of them are high-grade neoplasms. Prognostic factors in overall survival include tumor size, location and histologic grade. Examples of well-differentiated (low-grade) intraosseous osteosarcomas of the jaws (WDIOJ) have been rarely reported. This article presents two cases of this unusual lesion, one of which was located in the maxilla of a 17-year-old man and the other developed in the mandible of a 37-year-old woman. CT scan was necessary to detect the small foci of penetration into the thinned cortical bone and the reactive periosteal bone formation, which are important findings to establish the correct diagnosis of WDIOJ and help to exclude other benign intraosseous lesions that may be very similar histologically, such as fibrous dysplasia, ossifying and desmoplastic fibromas. In spite of tumor size (mean 5.2 cm), their well-demarcated borders allowed complete removal of both tumors. There is no evidence of tumoral activity in any of our patients after follow-up periods of 15 months and 5 years. Wide excision seems to be the treatment of choice for this subgroup of osteosarcomas.

p53, p21, Rb, and MDM2 proteins in tongue carcinoma from patients < 35 versus > 75 years.

Relatively rare squamous cell carcinomas of the tongue in young patients may be associated with different etiologic factors and pathogenetic mechanisms than carcinomas from the same site in older patients. Alterations in cell cycle proteins likely contribute to the biologic behavior of these neoplasms. The purpose of this investigation was to evaluate cell cycle proteins (p53, p21, Rb, MDM2) in lateral tongue cancers from patients at the two ends of the age spectrum. All available archived lateral tongue carcinomas from patients < 35 years (n = 36, 23 males and 13 females) were sectioned, immunohistochemically stained, and evaluated. Protein expression was scored as percent positive nuclei. An equal number of sequentially accessioned lateral tongue specimens from patients > 75 years (23 males and 13 females) were stained and compared. Positive p53 staining was seen in 18/36 of the < 35-year group versus 24/36 of the > 75-year group (p = 0.149). Increased p21 staining (both percent of positive cells and intensity) was evident in 25/32 of the < 35-year group versus 24/32 of the > 75-year group (p = 1.0). Increased p21 expression was seen in both p53-positive and -negative cases in both age groups. Rb protein was increased in 16/29 of the < 35-year group versus 17/26 of the > 75-year group (p = 0.58). Fourteen cases (4/35 vs 10/36, p = 0.135) showed positive MDM2 staining; MDM2-positive cases were also p53 positive in 4/4 younger and 8/10 older patients. We conclude that p53, p21, Rb, and MDM2 are over-expressed in lateral tongue cancers, and that immunohistochemical profiles are heterogeneous. A p53-independent pathway of p21 induction is supported by the results; p53 suppression may be associated with MDM2 protein expression in a subset of cancers. Significant differences in the expression of p53, p21, Rb, and MDM2 proteins are not evident in lateral tongue carcinomas from patients < 35 years as compared to patients > 75 years.

Histopathological diagnosis of biopsy samples from early esophageal carcinoma.

Carcinoma of the esophagus is frequently diagnosed in advanced clinical stages. When an esophagic carcinoma has infiltrated the submucosa or the muscular or serosa, metastases are a common finding. Thus, early diagnosis and opportune treatment are vital for patients with this type of neoplasm. Timely diagnosis can be done through endoscopic or X-ray studies and confirmed through a histopathological study by directed biopsy. We presently report the case of a 65 year old man with precedents of achalasia who underwent an endoscopic study using the Lugol staining technique for suspected malignant lesion classified as 0-IIc. After two biopsies it was diagnosed as early carcinoma of the esophagus and was subjected to mucosectomy. Histopathological findings are reviewed at architectural and cellular level and are essential to establish the diagnosis of early neoplastic lesions of the esophagus epithelium. These cellular changes are corroborated by immunohistochemical studies with nuclear expression of p53. The relevant literature was reviewed and experiences by Japanese and North American pathologists compared with emphasis on the need for multidisciplinary management to make an early diagnosis by endoscopic studies, Lugol staining, X-rays, biopsy and conservative treatment based on mucosectomy.

Tumor angiogenesis as a prognostic factor in oral cavity carcinomas.

Currently, lymph node metastasis and thickness of the tumor are the gold standard as a predictor of survival in patients with oral cavity squamous cell carcinoma (OSCC). However, there is a significant correlation between microvessel density and the development of cervical metastases or recurrence. Previous studies have demonstrated that head and neck cancers are able to induce an angiogenic response in experimental models. This factor shows a strong correlation with regional recurrence. In this study we propose to use angiogenesis as an independent prognostic indicator of recurrence. We evaluated the expression of tumor angiogenesis in OSCC and determinated its possible usefulness as a prognostic factor. Thirty-three cases with diagnosis of OSCC were identified from January 1985 to January 1997 in the Head and Neck Department of the Instituto Nacional de Cancerología in Mexico City. These cases were analyzed retrospectively for a minimum period of six months. All of them received a conventional complete treatment to the primary tumor and lymph node metastasis. Paraffin-embedded tumor specimens were available in all patients. The tumors were scanned and the areas of highest microvessel density (MVD) were immunostained for CD-34 using QBEnd/10 antibody. Statistical analysis included descriptive statistics, Wilcoxon test curves, and Cox's proportional hazards model for multivariate analysis. We identified 33 patients with OSCC, 16 were men and 17 women. The mean age among all patients was 58.9 years old. Based on tumor size 33.3% were T1, 27.3% T2, 12.1% T3, and 27.3% T4. The median microvessel count was 32.5. The mean percentage of MVD was 37 in patients with regional recurrence and in those patients without regional metastasis was 29 (p<0.05). 57.9% of the patients who presented recurrence had vessel counts over the median (p<0.01). In fact, 6 patients (46%) who showed more than 20% of angiogenesis expression and higher MVD presented with recurrence. Only 3 patients (23%) who had less than 20% of angiogenesis expression and lower MVD developed recurrence (p<0.01). Higher MVD was seen with increasing T and N stages; however, it did not show correlation with survival. In this study, angiogenesis expression demonstrated to be an independent factor of recurrence in patients with OSCC. It is suggested that it should be used as an independent prognostic indicator. In concordance with previous reports, we observed a significant correlation between MVD determination and recurrence of the tumor, followed by lymph node metastases and tumor size.

Repeat hepatic resection for recurrent metastatic melanoma.

We present an unusual case of a recurrent metastatic hepatic melanoma that had undergone a repeat hepatic resection. A 62 year-old female patient was diagnosed with a plantar melanoma and was managed with resection and regional lymphadenectomy. Eight months later, a solitary liver metastasis was diagnosed and a right hepatectomy performed. Sixteen months later, a recurrent solitary metastasis was diagnosed in the caudate lobe and resection was performed. She has since been asymptomatic with no evidence of recurrence of the disease at a 2-year follow up. We recommend surgical removal of hepatic metastatic melanoma in selected cases where the disease is confined to the liver and surgery can be performed without unacceptable risk.

Odontogenic tumors in Mexico: a collaborative retrospective study of 349 cases.

Reports about the frequency of odontogenic tumors are scarce, and diagnostic criteria used in the reports are not uniform. This article presents the results of a retrospective study of odontogenic tumors recorded in four services of diagnostic pathology in Mexico City (two dental schools, one cancer hospital, and one private oral pathology service). The final diagnosis in each case was based on the 1992 histologic criteria of the World Health Organization. The frequency of odontogenic tumors, expressed as a percent of all oral and maxillofacial specimens, ranged from 0.8% in the cancer hospital (0.02% of all biopsies) to 3.7% in the private oral pathology service. The frequency was identical for the two dental schools (2.5%). We found a total of 349 odontogenic tumors; of these, 345 were benign (98.8%), and 4 (1.1%) were malignant (3 were primary intraosseous carcinomas and 1 was a malignant ameloblastoma). The most frequently occurring tumors were odontoma (34.6%), ameloblastoma (23.7%), myxoma (17.7%), adenomatoid odontogenic tumor (7.1%), and calcifying odontogenic cyst (6.8%). Although relatively rare, odontogenic tumors are still an important cause of extensive surgical procedures in Mexico.

[Expression of cathepsin D in breast cancer and its clinical and histopathological correlations]. / Expresión de catepsina D en carcinoma mamario y sus correlaciones clínicas e histopatológicas.

BACKGROUND: Cathepsin D is a lysosomal protease which is overexpressed in some cases of breast cancer. Several studies done in tumor cytosol have shown that high levels of cathepsin D are associated with poor prognosis in patients with breast cancer but the results are not conclusive using immunohistochemistry methods to assay cathepsin D. OBJECTIVE: To evaluate if cathepsin D, assayed by a immunohistochemical technique using a polyclonal antibody, can be considered an independent prognostic factor in breast cancer. PATIENTS AND METHODS: Paraffine embedded sections of 68 tumor specimens from breast cancer patients in stages I to IV seen at the Instituto Nacional de Cancerologia during the period from 1985 to 1986. RESULTS: From the 68 patients, 35 (51%) had an intense positive staining for cathepsin D, 19 (28%) han mild staining and 14 (21%) were negative. Ten patients with mild staining had artifacts due to deficiencies in the tissue fixation technique. Cathepsin D expression did not have a prognostic value nor association with other clinical and histopathological prognostic factors well established in breast cancer. CONCLUSION: Cathepsin D determined by immunohistochemistry has no prognostic value in breast cancer.

[Laparoscopic partial hepatectomy. Report of the first case in Mexico]. / Hepatectomía parcial por laparoscopia. Informe del primer caso en México.

The authors report the case of a 47-year-old female patient referred to the Instituto Nacional de Cancerología with abdominal pain and a focal liver lesion in the left lateral segment. After a careful tumor work-up, a laparoscopic left lateral segmentectomy was performed. The postoperative course was uneventful and the patient was discharged at the 2nd postoperative day. Histologic examination revealed focal nodular hyperplasia. In a search of the literature we find this to be the first case treated by this approach in Mexico.

[Angiomyolipoma of the liver not associated with tuberous sclerosis]. / Angiomiolipoma de hígado no asociado a esclerosis tuberosa.

Angiomyolipoma is a rare benign mesenchymal tumor of the liver. We present the case of a 32-year-old female patient that seeks medical consultation to confirm pregnancy. Ultrasound was performed and a hyperechoic lesion was detected in the left lobe of the liver. CT scan showed a heterogenic mass arising from the left lobe of the liver, fine needle aspiration biopsy was performed and diagnosis of liposarcoma was made. A laparotomy was done and a left lateral segmentectomy performed, postoperative course was uneventful. Histology and immunohistochemical analysis of the tumor revealed classical findings of primary angiomyolipoma of the liver. This case shows the difficulty often found when a preoperative diagnosis of fatty liver lesions is made. A literature review is presented and the diagnosis and management of these lesions is discussed.

Prognostic factors and recurrence in breast cancer: experience at the national cancer institute of Mexico.

The purpose of this study was to analyze the prognostic and predictive factors that relate to locoregional or distant recurrences in breast cancer patients who have been treated at the National Cancer Institute of Mexico. Multivariate, time-dependent Cox regression analyses indicate that the pN status (positive versus negative lymph node; P = 0.003; HR (hazard ratio), 3.47; CI (confidence interval), 1.52-7.91) and the pathological complete response of the patient to neoadjuvant chemotherapy (yes versus no; P = 0.061; HR, 0.38; CI, 0.14-1.04) were important prognostic factors for recurrence.

Immunoexpression of matrix metalloproteinases and their inhibitors in different areas of oral squamous cell carcinoma.

BACKGROUND: Several studies have shown the participation of MMPs in oral squamous cell carcinoma, the most frequent malignant neoplasm of the oral cavity. The expression of some MMPs correlates with a more aggressive biological behaviour. The objective of this study was to determine which MMPs and TIMPs were expressed in both neoplastic and peritumoural stromal cells in different histopathology areas. METHODS: Patients who underwent primary tumour neck dissection for oral squamous cell carcinoma were included. Immunoexpression of MMP-1, -2, -3, -7, -9, -11, -13, and TIMP-1 and -2 in different areas of pathologic specimens (in situ carcinoma, primary tumour, invasive front, distant invasion carcinoma, and lymph node metastasis) was evaluated. Enzyme expression on mucosa adjacent to tumour served as control. RESULTS: Thirty cases were included. Only 6 MMPs and 1 TIMP were expressed in the studied areas. Statistically significant differences in the number of cases with positive MMPs or TIMP expression, in both neoplastic and peritumoural cells, between control and the rest of the areas were observed. MMP-2 expression was constant in the areas with a more aggressive biological behaviour. CONCLUSIONS: MMP-2 expression may represent a dynamic interaction between host and tumour that favours the establishment of neoplastic cells at distant sites.