p16INK4a and pRb expression in laryngeal squamous cell carcinoma with and without infection by EBV or different genotypes of HPV: a retrospective study.

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) represents one of the principal tumors of the head and neck. Human papillomavirus (HPV) and Epstein-Barr virus (EBV) are considered risk factors for the development and the clinical prognosis of LSCC. High levels of p16INK4a are suggested as a surrogate marker of HPV or EBV infection in some head and neck tumors but in LSCC is still controversial. Furthermore, pRb expression may be considered an additional biomarker but it has not been clearly defined. This work aimed to compare the expression of pRb and p16INK4a as possible biomarkers in tumor tissues with and without infection by EBV or different genotypes of HPV from patients with LSCC. METHODS: Tumor samples from 103 patients with LSCC were previously investigated for the presence and genotypes of HPV using the INNO-LiPA line probe assay and for the infection of EBV by qPCR. p16 INK4a and pRb expression was assessed by immunohistochemistry. RESULTS: Of the 103 tumor samples, expression of p16INK4a was positive in 55 (53.4%) and of this, 32 (56.1%) were positive for HPV whereas 11 (39.3%) were EBV positive but both without a significantly difference (p > 0.05). pRb expression was positive in 78 (75.7%) and a higher frequency of this expression was observed in HPV negative samples (87.0%) (p = 0.021) and in high-risk HPV negative samples (85.2%) (p = 0.010). No difference was observed when comparing pRb expression and EBV infection status (p > 0.05). CONCLUSION: Our results support the suggestion that p16INK4a is not a reliable surrogate marker for identifying HPV or EBV infection in LSCC. On the other hand, most of our samples had pRb expression, which was more frequent in tumors without HPV, suggesting that pRb could indicate HPV negativity. However, more studies with a larger number of cases are required, including controls without LSCC and evaluating other molecular markers to determine the real role of p16INK4a and pRb in LSCC.

Differential expression of mast cell granules in samples of metastatic and non-metastatic colorectal cancer in patients.

Various cell types participate in the tumor process, in which the mast cells have been described; however, the role they play in colorectal adenocarcinoma has not yet been fully understood. Therefore, the present work aimed to compare employing histochemistry and immunohistochemistry, the number of mast cells and the content of some cytoplasmic granules in moderately differentiated non-metastatic and metastatic colorectal adenocarcinoma, analyzing tissue samples from patients. Histochemical techniques with Toluidine Blue (TBO), Periodic Schiff Acid (PAS), Alcian Blue/Periodic Acid-Schiff (PAB) and Alcian Blue/Safranin (ABS); as well as immunohistochemical reactions with anti-antibodies anti-Tryptase and anti-Chymase were applied to quantify total mast cells and content of some cytoplasmic granules. Statistical analysis was performed using SPSS V22.0 software (p ≤ 0.05). The degree of positivity of the reaction and degranulation of mast cells was reported in percentages. In our results, we observed that there are differences in the quantity and histochemical composition of the granules of mast cells (metastatic group PAS and ABS comparing the TBO reaction), as well as in the immunohistochemical composition between Tryptase and Chymase and the number of degranulated cells in both study groups (74 % degranulated mast cells in the metastatic group, 66 % integrate mast cells in the non-metastatic group). Therefore, we consider that the differences may be some of the probable factors that lead to metastasis of colorectal adenocarcinoma.

First report of a Mexican family with mutation in the CDH1 gene.

BACKGROUND: Germline mutations in E-cadherin (CDH1) gene are associated with autosomal-dominantly inherited cancer syndrome characterized by diffuse gastric cancer, lobular breast cancer, and in some families, cleft lip/palate. However, there may be generations in which these neoplasms do not occur at all in a family and later on, one or another carcinoma arises, which makes it difficult for physicians to think about hereditary origin. METHODS: We report the first Mexican family with CDH1 mutation (variant c.377del). RESULTS: An asymptomatic young woman underwent a search for mutations in susceptibility genes for breast cancer due to the history of this neoplasm in her mother and maternal aunt. A CDH1 mutation was detected. After an endoscopy, a diffuse gastric carcinoma was found. Later on, three generations of this family were studied. The findings are presented. CONCLUSION: Medical communities should be aware of the contribution of this gene in the development of hereditary diffuse gastric carcinoma (HDGC) and breast cancer.

Infection and coinfection by human papillomavirus, Epstein-Barr virus and Merkel cell polyomavirus in patients with squamous cell carcinoma of the larynx: a retrospective study.

BACKGROUND: Human papillomavirus (HPV) is recognized as an important risk factor for laryngeal carcinogenesis. Although HPV-16 and 18 have been strongly implicated, the presence of other high-risk HPV (HR-HPV) genotypes or the coinfection with Epstein-Barr virus (EBV) or Merkel cell polyomavirus (MCPV) may increase the risk, but their etiological association has not been definitively established. METHODS: We characterized the genotype-specific HPV and the frequency of EBV and MCPV infections through the detection of their DNA in 195 laryngeal specimens of squamous cell carcinoma (SCC) histologically confirmed. RESULTS: HPV DNA was detected in 93 (47.7%) specimens. HPV-11 was the most frequent with 68 cases (73.1%), and HPV-52 was the most frequently HR-HPV found with 51 cases, which corresponds to 54.8% of all HPV-positive specimens. EBV DNA was detected in 54 (27.7%) tumor tissue specimens of which 25 (46.3%) were in coinfection with HPV. MCPV DNA was detected only in 11 (5.6%) cases of which 5 (45.4%) were in coinfection with an HR-HPV. No association between the presence of DNA of the three examined viruses and the patient smoking habits, alcohol consumption, age, the keratinization status, differentiation grade, or localization of the tumor in the larynx were found. DISCUSSION: HPV-52 was the most prevalent HR-HPV, which may suggest that this and other genotypes in addition to HPV-16 and 18 could be considered for prophylaxis. However, further studies including non-cancer larynx cases and the evaluation of other molecular markers and viral co-infection mechanisms are needed to determine the role of the different HR-HPV genotypes, EBV, and MCPV in the etiology of SCC of the larynx.

Células cebadas y sus patrones de expresión del receptor c-kit (CD117) como probables indicadores de metástasis en el adenocarcinoma de mama en humanos / Mast cells and expression patterns of c-kit (CD117) receptor as probable indicators of metastases in human breast adenocarcinoma

El adenocarcinoma de mama es la segunda neoplasia maligna más común en mujeres, solo después del cáncer de pulmón. Este tumor se clasifica histopatológicamente en bien, moderado y poco diferenciado. Además de esta clasificación, los análisis actuales utilizan inmunohistoquímica para identificar receptores hormonales para estrógenos y progesterona (RH) y HER2/neu, esta información permite hacer un pronóstico de respuesta al tratamiento y tiempo de sobrevida. Las células cebadas se han asociado a un mal pronóstico, ya que participan en la angiogénesis y el crecimiento tumoral favoreciendo la metástasis. Esto disminuye la esperanza de vida. También las células cebadas expresan en la membrana plasmática el receptor c-Kit (CD117) que se ha asociado a proliferación celular. En este estudio, se evaluó si existen variaciones en los patrones de expresión de c-Kit en las células cebadas presentes en muestras de adenocarcinoma de mama; y si los distintos patrones del receptor se asocian a la presencia de metástasis linfática. Se utilizaron muestras de adenocarcinoma moderadamente diferenciado, y se analizaron empleando métodos histológicos, histoquímicos e inmunohistoquímicos. Los grupos se clasificaron de acuerdo a su positividad a RH y HER2/neu, y se subclasificaron de acuerdo a la presencia o no de metástasis. Además se realizó un análisis morfométrico de células cebadas y los patrones de expresión de c-Kit. Los grupos con metástasis mostraron mayor cantidad de células cebadas comparados con el grupo control, y su grupo correspondiente sin metástasis. Las células cebadas con patrones de expresión 1 y 3 fueron más abundantes en los grupos con metástasis. En los grupos sin metástasis predominaron las células cebadas con el patrón 2. Los resultados sugieren que el número de células cebadas y los patrones de expresión de c-Kit, podrían ser empleados como indicadores probables, más no definitivos de la presencia de metástasis linfática.

Breast adenocarcinoma is the second most common neoplasm, just after lung cancer in women. According to histopathological features this tumor is classified into well, moderate and poorly differentiated. In addition to this classification, current analysis also use immunohistochemistry to detect estrogen and progesterone receptors (RH), and HER2/neu, this information is useful to make a prognostic in treatment response and survival time. Mast cells have been associated with bad prognosis, because they participate in angiogenesis and tumor growth promoting metastases. This decreases life expectancy. Also mast cells express in the plasmatic membrane the receptor c-Kit (CD117) that is associated to cell proliferation. In this study, we evaluated if there are variations in the expression patterns of c-Kit receptor in mast cells present in breast adenocarcinoma samples; and if expression patterns are associated with the presence of metastases to ganglion. Samples of moderately differentiated adenocarcinoma were evaluated using histological, histochemistry and immunohistochemistry methods. Groups were classified according to their positivity to RH and HER2/neu, and subclassified if presented or not metastases. Also mast cells and expression patterns of c-Kit receptor were analyzed by a morphometric method. Groups with metastases showed higher amount of mast cells, compared with control group and their corresponding group without metastases. Mast cells with expression patterns 1 and 3 were more abundant in all the groups with metastasis. In groups without metastases mast cells with pattern 2 were predominant. Results suggest that the amount of mast cells and the expression patterns of c-Kit could be use as probable indicators, but not definitive of the presence of nodal metastases.

[Renal metastasis of classic seminoma]. / Metástasis renal de seminoma clásico.

INTRODUCTION: Seminoma comprises approximately 50% of testicular germ cell tumors. Renal metastases are infrequent, and are usually recognized at necropsy. CLINICAL CASE: A 24 years-old man with history of left radical orchiectomy due to classical seminoma (stage I), and adjuvant radiotherapy, showed elevated levels of beta-human chorionic gonadotropin and lactate dehydrogenase in the eleven month follow-up. Computed tomography showed a 9 × 8 cm lobulated, heterogeneous tumor in the left kidney. The histopathological and immunohistochemical assay demonstrated a classical metastatic seminoma. CONCLUSION: The majority of renal tumors represent primary neoplasm; in patients with extra-renal tumors we must consider the possibility of a metastatic disease.

[A case of small-cell malignant melanoma in a pregnant patient]. / Melanoma maligno de células pequeñas en el embarazo.

INTRODUCTION: Malignant melanoma (MM) is an aggressive neoplasm that may affect pregnant women. Malignant melanoma with small-cell morphology (MMSCM) is a rare variant of MM that can cause confusion in its diagnosis. OBJECTIVE: To report a fatal case of MMSCM in a pregnant woman, highlighting immunohistochemistry (IHC) as a very useful tool in the final diagnosis. CLINICAL CASE: A 22-year-old pregnant female presented with a 5-cm cutaneous tumor in her right leg. The lesion was excised but the patient refused any further therapy. The natural outcome of this neoplasm occurred with local recurrence and multiple metastases to the lungs, liver, and kidneys. CONCLUSIONS: MM should be included in the differential diagnosis of small-cell cutaneous tumor, and IHC is mandatory for diagnosis confirmation. The recommended suggested screening includes, as a minimum, one sensitive marker (S-100 protein) and one specific (HMB45) marker for melanogenesis.