Gastric cancer is the second cause of death by cancer worldwide.1 In 2012, the World Health Organization estimated about one million new cases of gastric cancer (952,000 cases, 6.8% of all cancers), putting it in fifth place for malignant neoplasias, after lung, breast, colorectal, and prostate cancers; more than 70% of the cases (677,000 cases) occurred in developed countries (456,000 cases in men; 221,000 in women) and half of those cases were on the Asian continent (mainly China)2

For the year 2011 in Mexico, gastric cancer was among the main causes of hospital morbidity in men, with the highest rate in the 75 to 79-year-old population (47 of every 100,000 men in that age group), followed by the 65 to 74-year-old population (38 of every 100,000 men of that age group). It is currently known that of the main malignant tumors causing death in the Mexican population of 20-year-olds, gastric cancer is the 3rd cause in both women (7%) and men (8.6%), after breast cancer (13.8%), cervical cancer (10.4%), prostate cancer (16.9%), and bronchial/lung cancer (12.8%), respectively.3

According to Lauren, gastric adenocarcinoma is a heterogeneous disease that is histologically divided into the intestinal, diffuse, and undifferentiated non-mucus-producing types,4 and is anatomically classified as proximal or distal.5 More recently, genomic and molecular classifications have been made,6–8 and numerous molecular alterations may be involved in each histologic subtype. Anatomic and histologic classification can provide knowledge about tumor biology and facilitate the selection of a population to receive targeted therapies.9

Gastric cancer development is a multifactorial and complex process with a lengthy progression. It is very unlikely that infection by Helicobacter pylori alone is responsible for the development of gastric cancer. There is evidence that the consumption of salty foods, N-nitroso compounds, and a low consumption of fresh fruit and vegetables increase the risk for gastric cancer.10

Intestinal-type adenocarcinoma is associated with severe atrophic chronic gastritis, intestinal metaplasia, and dysplasia. It corresponds to well or moderately differentiated carcinomas, and is characterized by the formation of glandular cells similar to intestinal cells. It is mainly situated in the antrum and settles in zones of previous intestinal metaplasia, especially of the colonic or incomplete type.11 Diffuse-type adenocarcinoma encompasses the infiltrative variety and is poorly differentiated, with the presence of signet ring cells and without apparent gastritis. It is thought to appear de novo and is associated with low CDHI regulation.12 There are no epidemiologic studies on the Mexican population that classify gastric adenocarcinoma by histologic subtype, in the knowledge that each subtype behaves differently.

The aim of this study was to determine the frequency of gastric adenocarcinoma and compare the histopathologic characteristics of its subtypes reported at the Hospital Juárez de México (a tertiary care center) over the last 10 years.

A total of 417 cases of gastric adenocarcinoma were found. Three hundred and thirty-four (80%) of them were obtained through endoscopic biopsy and 83 (20%) through gastrectomy (51 partial, 26 total, and 6 not specified). Diffuse-type adenocarcinoma was reported in 230 patients (55.2%), intestinal-type in 118 patients (28.2%), and undifferentiated-type in 25 patients (6%); sub-type was not determined in 44 patients (10.6%) (figure 1). The mean age for the diffuse-type patients was 54.02±14.93 and 118 of those patients (51.3%) were men. The mean age for the patients with the intestinal type was 63.43±13.78, and 69 (62.2%) were men.

Figure 1.

Number of cases divided by sex and histologic type.

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The diffuse type had a statistically significant association in relation to the number of cases in patients < 50 years of age (p<0.001), perineural invasion (p=0.5), positive surgical margins (p<0.5), and positive angioinvasion (p<0.5).

Among the diffuse-type patients, 92 were under 50 years of age, compared with 22 patients with intestinal-type carcinoma (figure 2).

Figure 2.

Number of cases divided by age group and histologic type.

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Analyzing the histologic subtypes of gastric adenocarcinoma in patients diagnosed over the last 10 years at the Hospital Juárez de México, the diffuse-type was observed to be the most prevalent, presenting in one-third of the patients under 50 years of age.

There are no studies in Mexico that classify adenocarcinoma by subtype or anatomic location. In a study by Bonequi et al.,13 they carried out a search of the PubMed database and reported that in 9 out of 20 Latin American countries, including Mexico, the histologic gastric adenocarcinoma subtype encountered was the intestinal-type in the distal location (figure 3). There are high incidence rates of gastric cancer in Latin America, but the reasons for this are not yet known. Convincing data suggest environmental factors and certain diseases, such as atrophic gastritis,14 adenomatous polyps,15 dysplasia,16 metaplasia,17 Ménétrier's disease,18 and pernicious anemia.19 Also included are nutritional factors, such as high salt intake and the consumption of smoked foods, spicy foods, nitrite-rich foods, foods high in carbohydrates and fat, and the low consumption of milk, fresh fruit and vegetables, selenium, and vitamins A, C, and E.20 High tobacco and alcohol consumption as risk factors for gastric cancer are still a subject of debate.21,22

Figure 3.

H&E stain; intestinal-type adenocarcinoma.

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Numerous researchers have reported a worse prognosis for patients with proximal cancer than those with cancer that is located in the mid and distal regions of the stomach.23 Despite the fact that the global incidence of gastric cancer continues to decrease, the incidence of proximal and gastroesophageal junction gastric adenocarcinoma in the U.S. is increasing.24,25

The development of molecular biology has improved our understanding of gastric cancer, even though its molecular mechanisms are not yet known. Some interesting molecules have been suggested as prognostic markers in these patients, including cell adhesion molecules.26 Multiple pathways are involved in different subtypes: human epidermal growth factor receptor 2 (HER2)27 and epidermal growth factor receptor28 overexpression predominate in non-diffuse cancer. Diffuse-type gastric cancer is characterized by aberrant cell adhesion (figure 4). Cadherins, together with catenins, play an important role in cell adhesion and polarity.29 Defects in the APC and DCC genes, microsatellite instability, and promoter hypermethylation of the hMLH1 gene have been associated with intestinal-type gastric cancer.30–33 Tumor suppressing genes, such as p53,34 and overexpression of the epidermal growth factor receptor, vascular endothelial growth factor receptor, and HER2 have all been associated with poor outcome.35,36 Targeted therapies combined with chemotherapy have produced encouraging results in the treatment of patients with advanced esophageal and gastric cancer.37

Figure 4.

H&E stain; adenocarcinoma with signet ring cells.

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Patients of different racial and ethnic groups, whatever their origins, have different natural histories, detection and treatment access, as well as dissimilar outcomes, in relation to numerous diseases.38 These variations have an important value because they enable the identification of biologic, environmental, and socioeconomic differences. The understanding of the biologic and molecular basis of gastric cancer can facilitate oncologic therapy adapted to the individual characteristics of each specific tumor.

Ours is the first study on the Mexican population to highlight the differences between the histologic subtypes of gastric adenocarcinoma, which could facilitate the selection of targeted therapies. The most frequent gastric cancer subtype in our population was the diffuse-type, which is associated with worse outcome. Up to one-third of the patients with gastric adenocarcinoma were under the age of 50 years, which has significant economic implications. The histology, sex, and age at time of presentation justify further research on the epidemiology, pathogenesis, and molecular biology of gastric cancer in Mexico.

No financial support was received in relation to this study.

The authors declare that there is no conflict of interest.