Pure micropapillary rectal carcinoma with CK7 and CK20 coexpression and loss of CDX2 reactivity / Carcinoma micropapilar rectal puro con coexpresión de CK7 y CK20 y pérdida de reactividad CDX2

The micropapillary carcinoma is regarded as an aggressive variant of adenocarcinoma in any location. Histologically is characterized by papillary cell clusters surrounded by clear spaces. The reported proportion of micropapillary carcinoma component to the entire tumor ranged from 5 to 80 percent and no pure cases has been reported. There are near of 130 cases reported to date in colorectum. We experienced a patient with a pure micropapillary carcinoma showing coexpression of CK7, CK20, and absence of CDX2, which had an aggressive neoplasm with extense perineural, vascular and lymphatic invasion also extensive nodal metastasis. The presence of a micropapillary carcinoma in the colorectum seemed to be closely related with nodal metastasis, similar to the case for micropapillary carcinomas in other organs. Therefore, if a micropapillary component is identified in a tumor, particularly in a biopsy specimen, even if the pre-operative diagnosis is a pedunculated early colorectal cancer, should be carefully consider the extent of surgical resection due to the high potential for nodal metastasis.

El carcinoma micropapilar es considerado como una variante agresiva del cáncer en cualquier localización. Histológicamente se caracteriza por grupos de células papilares rodeada de espacios libres. Se informó que la proporción del componente carcinoma micropapilar en la totalidad de un tumor varió entre 5 por ciento a 80 por ciento y no se han reportado casos puros. Existen cerca de 130 casos reportados hasta la fecha en colon y recto. Se describe el caso de un paciente con un carcinoma micropapilar puro que muestra coexpresión de CK7, CK20, y la ausencia de CDX2, que tenía un tumor agresivo con extensa invasión perineural, vascular y linfática además de metástasis nodular extensa. La presencia de un carcinoma micropapilar en la región colorrectal parece estar estrechamente relacionada con metástasis nodular, similar al caso del carcinomas micropapilar en otros órganos. Por lo tanto, si un componente micropapilar se identifica en un tumor, sobre todo en una muestra de biopsia, incluso si el diagnóstico pre-operatorio es un cáncer colorrectal temprano pediculado, se debe considerar cuidadosamente la extensión de la resección quirúrgica debido a la alta probabilidad de metástasis nodular.

Correlation between total nitrite/nitrate concentrations and monoamine oxidase (types A and B) and semicarbazide-sensitive amine oxidase enzymatic activities in human mesenteric arteries from non-diabetic and type 2 diabetic patients

The aim of this study was to determine the correlation between total nitrite/nitrate concentrations (NOx) and the kinetic parameters of monoamine oxidase enzymes (MAO-A and MAO-B) and semicarbazide-sensitive amine oxidase (SSAO) in human mesenteric arteries. Arteries were from non-diabetic and type 2 diabetic patients with sigmoid or rectum carcinoma for whom surgery was the first option and who were not exposed to neo-adjuvant therapy. Segments of human inferior mesenteric arteries from non-diabetic (61.1 ± 8.9 years old, 7 males and 5 females, N = 12) and type 2 diabetic patients (65.8 ± 6.2 years old, 8 males and 4 females, N = 12) were used to determine NOx concentrations and the kinetic parameters of MAO-A, MAO-B and SSAO by the Griess reaction and by radiochemical assay, respectively. The NOx concentrations in arteries from diabetic patients did not differ significantly from those of the non-diabetic group (10.28 ± 4.61 vs 10.71 ± 4.32 nmol/mg protein, respectively). In the non-diabetic group, there was a positive correlation between NOx concentrations and MAO-B parameters: Km (r = 0.612, P = 0.034) and Vmax (r = 0.593, P = 0.042), and a negative correlation with the SSAO parameters: Km (r = -0.625, P = 0.029) and Vmax (r = -0.754, P = 0.005). However, in the diabetic group no correlation was found between NOx concentrations and the three kinetic parameters of the enzymes. These results suggest an important function of sympathetic nerves and vascular NOx concentrations in arteries of non-diabetic patients. Thus, these results confirm the importance of a balance between oxidants and antioxidants in the maintenance of vascular homeostasis to prevent oxidative stress.

Changes in NAD/ADP-ribose metabolism in rectal cancer

The extent of ADP-ribosylation in rectal cancer was compared to that of the corresponding normal rectal tissue. Twenty rectal tissue fragments were collected during surgery from patients diagnosed as having rectal cancer on the basis of pathology results. The levels of ADP-ribosylation in rectum cancer tissue samples (95.9 ± 22.1 nmol/ml) was significantly higher than in normal tissues (11.4 ± 4 nmol/ml). The level of NAD+ glycohydrolase and ADP-ribosyl cyclase activities in rectal cancer and normal tissue samples were measured. Cancer tissues had significantly higher NAD+ glycohydrolase and ADP-ribosyl cyclase activities than the control tissues (43.3 ± 9.1 vs 29.2 ± 5.2 and 6.2 ± 1.6 vs 1.6 ± 0.4 nmol mg-1 min-1). Approximately 75 percent of the NAD+ concentration was consumed as substrate in rectal cancer, with changes in NAD+/ADP-ribose metabolism being observed. When [14C]-ADP-ribosylated tissue samples were subjected to SDS-PAGE, autoradiographic analysis revealed that several proteins were ADP-ribosylated in rectum tissue. Notably, the radiolabeling of a 113-kDa protein was remarkably greater than that in control tissues. Poly(ADP)-ribosylation of the 113-kDa protein in rectum cancer tissues might be enhanced with its proliferative activity, and poly(ADP)-ribosylation of the same protein in rectum cancer patients might be an indicator of tumor diagnosis.

Change of telomerase activity in rectal cancer with chemoradiation therapy

Telomerase, an enzyme associated with cellular immortality, is expressed by most malignant cells and is inactive in most normal somatic cells, with the exception of proliferative stem cells, germ cells and activated lymphocytes. Measuring telomerase activity clinically may provide useful diagnostic and prognostic information of cancer. The purpose of this study was to investigate the change in telomerase activity following chemoradiation in rectal cancer, which almost always produces positive enzymatic activity. A total of 24 tumor tissue samples were used in this study, consisting of 12 paired specimens before and 4 week after chemoradiation. Telomerase activity was determined by PCR-based telomeric repeat amplification protocol (TRAP) assay. The telomerase activity was positive in 10 out of 12 patients (83%) in pre-irradiated and post-irradiated states. The levels of telomerase activity was decreased in 8 out of 10 patients after chemoradiation (80%) and two cases showed no change in enzymatic activity. One case showed no activity in either sample. The other case showed no enzymatic activity in the pre-irradiated sample, but showed weak activity in the post-irradiated sample. These data indicate that telomerase activity in rectal cancer is reduced after neoadjuvant chemoradiation therapy, possibly suggesting a mechanism of downstaging following chemoradiation therapy in cancer.