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.

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.

[Prevalencia y genotipos del virus del papiloma humano en muestras de tejido laríngeo de pacientes con cáncer de laringe del noreste de México]. / Prevalence and genotypes of the human papillomavirus in laryngeal tissue samples of patients with laryngeal cancer from Northeastern Mexico.

ANTECEDENTES: El cáncer de laringe representa el 21.7% de las neoplasias malignas de vías aerodigestivas superiores. La prevalencia del virus del papiloma humano (VPH) en el cáncer de laringe oscila entre el 0 y el 80%. MÉTODO: Se incluyeron 112 muestras de tejido laríngeo de pacientes con cáncer de laringe. Se amplificó el ADN y se analizó la presencia y el genotipo del VPH mediante hibridación reversa (INNO-LiPA®). Se realizaron pruebas de ji cuadrada, Fisher y t de Student no pareada. RESULTADOS: Se incluyeron muestras de 107 hombres (95.5%) y 5 mujeres (4.5%), con una edad de 65.3 ± 10.1 años, con antecedente de tabaquismo 108 (96.4%), alcoholismo 9 (8.0%) y carcinoma epidermoide moderadamente diferenciado queratinizante 96 (85.7%). Se identificó VPH en 60 (53.5%), VPH-11 en 51 (45.5%), VPH-52 en 27 (24.1%), VPH-16 en 9 (8.0%), VPH-45 en 3 (2.6%) y coinfección por más de un genotipo en 31 (27.6%). No hubo diferencia entre pacientes con y sin infección por VPH en cuanto a edad, sexo, localización, diagnóstico histopatológico, tabaquismo ni alcoholismo (p > 0.05). CONCLUSIONES: La prevalencia de infección por VPH en el cáncer de laringe fue del 53.5%, con coinfección por más de un genotipo en el 27.6%. El genotipo más frecuente fue el VPH-11, tipo de bajo riesgo, seguido por el VPH-52, de alto riesgo oncogénico. BACKGROUND: Laryngeal cancer represents 21.7% of malignancies of the upper aerodigestive tract. The prevalence of the Human Papillomavirus (HPV) in laryngeal cancer ranges 0 to 80%. METHODS: We included 112 laryngeal tissue samples obtained from patients with laryngeal cancer. DNA was extracted and amplified by PCR. HPV presence and genotype were analyzed by the reverse hybridization INNO-LiPA® assay. Chi-square, Fisher's and unpaired Student t tests were used. RESULTS: Samples from 107 male (95.5%) and 5 female patients (4.5%) were evaluated, aged 65.3±10.1 years, 108 with smoking history (96.4%), 9 with alcoholism history (8.0%), and in 96 the histological diagnosis was moderately differentiated keratinizing squamous cell carcinoma (85.7%). HPV was detected in 60 samples (53.5%), HPV-11 in 51 (45.5%), HPV-52 in 27 (24.1%), HPV-16 in 9 (8.0%), HPV-45 in 3 (2.6%), and coinfection by more than one genotype in 31 (27.6%). There was no difference between patients with and without HPV infection with respect to age, sex, tumor location and histology, smoking and alcoholism history (p>0.05). CONCLUSIONS: The prevalence of HPV infection in laryngeal cancer was 53.5% with coinfection with more than one genotype in 27.6%. The most frequent genotype was HPV-11, an oncogenic low-risk genotype, followed by HPV-52, a high-risk genotype.

Leptin receptor expression during the progression of endometrial carcinoma is correlated with estrogen and progesterone receptors.

INTRODUCTION: The hormone leptin, which is produced in the adipose tissue, may influence tumorigenesis directly via its receptor (Ob-R). Thus, a role for Ob-R in endometrial carcinogenesis has been proposed. However, most studies neither included samples of the entire histological progression of endometrial carcinoma nor examined Ob-R jointly with the estrogen and progesterone receptors (ER and PR, respectively). MATERIAL AND METHODS: To determine the fluctuations of Ob-R, ER, and PR during the histological progression of endometrial carcinoma, we assessed their expression via immunohistochemistry (IHC) in six histological types of endometrium (proliferative, secretory, nonatypical and atypical hyperplasia, and endometrioid and nonendometrioid endometrial carcinoma), in which we performed histopathological and digital scoring for the quantification of receptors. RESULTS: We found that Ob-R expression was positively correlated with that of ER and PR (r = 1, p < 0.001; r = 0.943, p < 0.005, respectively), and there was a significant difference in Ob-R expression among proliferative normal endometrium, hyperplasias, and carcinomas, according to their relative digitally scored Ob-R expression (p < 0.001). In addition, we observed that Ob-R expression in the secretory endometrium was more similar to that of carcinomas than to its proliferative counterpart. CONCLUSIONS: These results indicate that Ob-R expression fluctuates during endometrial carcinogenesis in correlation with ER and PR, suggesting that Ob-R expression in vivo is highly dependent on estrogen and progesterone activities in the endometrium and on its ER and PR status, as suggested previously by in vitro studies.

[Neuroendocrine carcinoma of the urinary bladder. A case report]. / Carcinoma neuroendocrino de vejiga. Reporte de un caso.

BACKGROUND: Small cell carcinoma of the urinary bladder is an infrequent lesion. CLINICAL CASE: We present the case of a 68-year-old male who arrived at the emergency room with a history of 24-h gross hematuria. Imaging studies show a urinary bladder tumor with a 218 cc volume that during a 20-day period increased to 426 cc. Histopathological images with hematoxylin-eosin show an infiltrating solid mass with uneven borders. It is composed of neoplastic cells with evident nuclei predominance and scant cytoplasm (small cells). Chromogranin immunohistochemical staining shows a diffusely positive cytoplasmic granular pattern on neoplastic cells. High molecular weight cytokeratin staining shows a negative pattern on neoplastic cells along with a positive pattern on reporsurrounding normal urothelium. Tumoral mass is positive for synaptophysin and CD-56 and negative for CK-7 and CK-20. Patient therapy was based on radiation plus chemotherapy. CONCLUSION: Small cell carcinoma of the urinary bladder represents 0.35-0.70% of urinary bladder tumors. Histological and immunohistochemical identification are key elements in the diagnosis. Treatment approach is based on cisplatin-based chemotherapy plus radical cystectomy, except when metastatic disease is present.

Antecedentes: el carcinoma neuroendocrino de células pequeñas primario de vejiga es una lesión maligna muy poco frecuente. Caso clínico: paciente masculino de 68 años de edad, que tuvo hematuria macroscópica de 24 horas de evolución. Estudios de imagen mostraron tumoración vesical de 218 cc, que en 20 días alcanzó un volumen de 426 cc. A la tinción con hematoxilina-eosina, histológicamente se apreció: placa sólida infiltrante de bordes irregulares, compuesta por células neoplásicas con claro predominio de núcleo y escaso citoplasma (células pequeñas). A la tinción inmunohistoquímica con cromogranina parecía difusamente positivo en células neoplásicas, en un patrón granular citoplasmático. A la tinción con citoqueratina de alto peso molecular se observó patrón negativo en células neoplásicas con control interno positivo en el urotelio acompañante en espécimen. De igual manera, la tumoración fue positiva para sinaptofisina y CD-56 y negativa para CK-7 y CK-20. El paciente recibió tratamiento a base de radioterapia y quimioterapia. Conclusión: el carcinoma neuroendocrino de células pequeñas primario de vejiga representa de 0.35 a 0.70% de los tumores vesicales primarios. Su diagnóstico se basa en el reconocimiento histológico e inmunohistoquímico. El tratamiento se fundamenta en quimioterapia con cisplatino más cistectomía radical, excepto cuando existe enfermedad metastásica.

Expression of leptin receptor in endometrial biopsies of endometrial and ovarian cancer patients.

The adipokine leptin plays a critical role in the regulation of reproductive function and there has been growing interest in its potential role in the development of cancers in which obesity is an established risk factor. Serum leptin levels were found to be higher in patients diagnosed with endometrial and ovarian cancer compared to those observed in healthy individuals. This study was conducted to determine the expression of the leptin receptor (Ob-R) in endometrial biopsies of patients diagnosed with endometrial and ovarian cancer. In this preliminary study, immunohistochemistry (IHC) and the color deconvolution method were used to assess the expression levels of the Ob-R protein in three groups of endometrial tissue: one from patients diagnosed with endometrioid endometrial carcinoma, one from patients diagnosed with ovarian cancer and one from individuals without any diagnosed gynecologic disease (control group). Our results demonstrated that the highest expression of Ob-R protein in endometrial biopsies was detected in the ovarian cancer group (P=0.000). This finding suggests that changes in Ob-R expression may be assessed through the measurement of the optical density of endometrial biopsies and may become a useful tool in preventive screening, particularly for ovarian cancer.

Monosomy of chromosome 8 could be considered as a primary preneoplastic event in breast cancer: A preliminary study.

This pilot study analyzed and compared the presence of chromosome 8 aneusomy in Mexican women with breast cancer and adjacent, intraductal, proliferative lesions. To determine the chromosome 8 copy number, we performed fluorescence in situ hybridization in nine patients (1800 cells) who underwent mastectomy. We selected two tissue samples from each patient, one corresponding to the invasive ductal carcinoma (IDC) and the other adjacent to the intraductal proliferative lesion (IPL). Breast tissue from 17 autopsy samples (1700 cells) was used as a control. The number of cells with monosomy, disomy and polysomy per subject and type of tissue were compared among the three groups of tissue with the RxC statistical software package using 50,000 total replicates. Chromosome 8 aneusomy was found in 66 and 67% of cells from the IDC and IPL samples, respectively. Monosomy was detected significantly more frequently in IPL compared with IDC samples (49.11 vs. 27.11%; p=0.0000), whereas polysomy was significantly more frequent in IDC compared with IPL samples (40.11 vs. 16.99%; p=0.00000). Control cells showed 92.3% disomy. These findings suggest that polysomy of chromosome 8 is more frequently observed in IDC and that monosomy is more frequent in tissue of IPL. Therefore, monosomy may be considered as a primary preneoplastic event. Future studies should be performed to increase the amount of breast tissue with ductal proliferative changes and with cancer, in order to support the results of this pilot study.

Immunohistochemical analysis of prostate apoptosis response-4 (Par-4) in Mexican women with breast cancer: a preliminary study.

BACKGROUND AND AIMS: We undertook this study to compare the expression level of prostate apoptosis response-4 (Par-4) among patient outcome in two groups of women with breast cancer (short and long survival) and two groups without breast cancer (benign lesion and control). METHODS: We included breast specimens with nonhistological abnormalities (eight samples) as a control group. Semiquantitative and quantitative analysis of immunohistochemical staining by image analysis software were used to study the intensity of Par-4 expression. Both methods produced similar results (p>0.05). RESULTS: No significant expression of Par-4 was observed in normal breast tissue. Benign lesions and breast cancer tissue showed strong nuclear expression of Par-4, predominantly on epithelial cells and specifically in ductal cells. Par-4 expression was lower in myoepithelial cells and there was no appreciable stromal staining. Significantly less Par-4 reactivity was detected in tissue from patients with a short survival compared with patients with benign lesions and those with a long survival. CONCLUSIONS: Our findings suggest that a lower expression level of Par-4 is related to an unfavorable prognosis. A larger prospective study of samples of all patient groups with a longer follow-up is needed to validate this finding.

[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.

[Thyroid cancer in children and adolescents]. / Cáncer de tiroides en niños y adolescentes.

BACKGROUND: Thyroid nodules in children and adolescents may be associated to malignant neoplasms. Although thyroid cancer is a rare event in this age group, delayed diagnosis is associated to metastatic, regional or lung disease, but even in these circumstances appropriate treatment may be followed by good prognosis. We decided to review the clinical course of these patients in our hospital from 1980 to 2001. METHODS: We found fifteen patients younger than 18 years diagnosed with thyroid carcinoma, which had been followed by at least 12 months, with a mean of 95 months and a maximal of 10 years. All patients were treated by surgery and 131 iodine, and followed by scans, ultrasound and thyroglobulin analysis. RESULTS: The patients group were thirteen females and two males. At diagnosis, seven patients (46.7o%) had metastatic regional disease and eight had a thyroid nodule. Total thyroidectomy with a modified neck dissection and 131 iodine was the initial treatment for patients with regional disease and subtotal thyroidectomy and 131 iodine in the follow-up to treat the thyroid bed or metastases was the treatment for patients with localized disease. All patients had a histologic pattern of papillary carcinoma. Nine patients (60%) had local recurrence in a mean follow-up of 37 months, one patient that had been previously treated by total thyroidectomy and all patients that were treated by subtotal thyroidectomy, however, all responded to the complementary treatment. At this moment the mean follow up is 95 months and all the patients have survived. CONCLUSIONS: In our experience thyroid cancer in children and adolescents is a rare event whose delayed diagnosis is associated to regional lymph node or lung metastases. Subtotal thyroidectomy was associated to disease progression to metastases, but complementary treatment was successful and all patients have survived.

Mitogen-actived protein kinase activation is an early event in melanoma progression.

PURPOSE: Melanoma is the most common cause of death from cutaneous malignancy, and is the cancer that is most rapidly rising in incidence. Because current therapeutic methods for metastatic melanoma are poorly efficacious, enhanced understanding of signal transduction in melanoma progression is warranted. Prior experimental studies in murine models and human tissues have shown a correlation among activation of mitogen activated protein kinase (MAPK) signaling, angiogenesis, and tumorigenesis. Because of these findings, we wanted to assess the role of MAPK signaling in melanoma progression and angiogenesis. EXPERIMENTAL DESIGN: We studied expression of phosphorylated (active) MAPK and two target genes known to be induced by MAPK signaling, tissue factor and vascular endothelial growth factor, in 131 melanocytic lesions, ranging from atypical nevi to metastatic melanoma. RESULTS: We observed little staining for activated (phosphorylated) MAPK and low amounts of angiogenesis in atypical nevi, but angiogenesis and MAPK activation were activated in radial growth melanoma and in later stage lesions. CONCLUSIONS: Our findings implicate MAPK activation as an early event in melanoma progression, and MAPK may be a potential target for pharmacologic intervention.

Un caso de síndrome de Cushing por hiperplasia nodular pigmentaria primaria / A case of primary pigmented nodular edrenocortical disease

La hiperplasia nodular pigmentaria primaria es una causa rara de síndrome de Cushing, con predilección en adultos jóvenes del género femenino. En el laboratorio está caracterizada por un hipercortisolismo independiente de ACTH; en el estudio histopatológico por múltiples nódulos corticales pequeños y obscuros, de células grandes, citoplasma con eosinofilia y lipofuscina que le dan una particularidad distintiva; además puede encontrarse una atrofia internodular el tratamiento de elección es la adrenalectomía bilateral. En este reporte damos a conocer el caso de una mujer de 32 años de edad con hiperplasia nodular pigmentaria primaria; además presentamos una revisión de la literatura

Tumor seudosarcomatoso miofibroblástico de vejiga: informe de un caso y revisión de la literatura accesible / Myofibroblastic pseudosarcomatous tumor of the bladder. Report of a case and literature review

En años recientes se han descrito varias lesiones proliferativas de células fusiformes atípicas, que han imitado clínica y morfológicamente a sarcomas de partes blandas, en especial en las vías genitourinarias. Se han usado diferentes términos, como seudotumor inflamatorio, tumor fibromixoide seudosarcomatoso, entre otros. En la mayor parte de los casos los pacientes han tenido el antecedente de intervención quirúrgica o instrumentación de las vías urinarias. No obstante, en algunos pacientes jóvenes este antecedente ha sido negativo. De manera uniforme, en todos los casos la lesión ha tenido carácter infiltrativo local, sin ninguna prueba de enfermedad metastática o letal. Se presenta un caso único en el servicio en que trabajan los autores, que causó polémica diagnóstica y se trato con derivación urinaria y resección transuretral