Association between carbonic anhydrase 9 expression and poor prognosis in sinonasal squamous cell carcinoma.

OBJECTIVES: Carbonic anhydrase 9 (CA9), as a member of the carbonic anhydrase enzyme family, was an endogenous marker of hypoxia. Previous studies suggested CA9 expression was correlated with poor prognosis in multiple types of malignancies. Therefore, this study was to evaluate the role of CA9 in sinonasal squamous cell carcinoma (SNSCC) and to determine whether this biomarker was associated with patient clinicopathologic characteristics and prognosis. METHODS: We assessed 63 patients diagnosed with SNSCC in 2013-2017 who underwent curative surgery. Tumor specimens was immunohistochemically analyzed for CA9 expression. The expression levels of CA9 was evaluated in relation to clinicopathological factors and prognosis. RESULTS: Positive expression of CA9 was observed in 21 (33.3%) patients and was significantly correlated with local recurrence (p = 0.016), overall survival (OS) (p = 0.003) and disease-free survival (DFS) (p = 0.002). In Cox's multivariate analysis, CA9 expression was an independent negative prognostic factor for OS (p = 0.048) and DFS (p = 0.019). CONCLUSIONS: Our findings demonstrated that CA9 overexpression could be used as an independent prognostic biomarker and therapeutic target in SNSCC.

[Clinical differences between primary nasopharyngeal NK/T-cell lymphoma and primary nasal cavity NK/T-cell lymphoma with nasopharynx extension].

Objective: To investigate the clinical and prognostic differences between primary nasopharyngeal natural killer (NK)/T-cell lymphoma (NP NKTCL) and extranodal NK/T-cell lymphoma of the nasal cavity with nasopharynx extension (N-NP NKTCL). Methods: A total of 89 patients with NP NKTCL and 113 patients with N-NP NKTCL from January 2000 to June 2015 were retrospectively analyzed. Clinical and pathological features, treatment responses and prognosis were compared between the two groups. Results: NP NKTCL patients showed similar clinicopathological features with those with N-NP NKTCL, except that the former had a relative low proportion of elevated lactate dehydrogenase (LDH) levels (28.1% vs. 41.6%; P=0.001). Both of two groups presented with high proportion of cervical lymph node involvement (55.1% and 42.5%; P=0.076). The 5-year overall survival (OS) rates in these two groups were 63.2% and 54.6%, respectively, whereas 5-year progress-free survival (PFS) rates were 50.7% and 45.6%, respectively. For the patients with stage Ⅰ and Ⅱ, the 5-year OS and PFS rates in these two groups were 68.8% and 55.7% as well as 55.6% and 47.2%, respectively. These were no statistically significant differences between two groups (all P>0.05). The complete response (CR) rate after initial chemotherapy in NP NKTCL group was 43.8%, which was significant higher than that of 19.6% in N-NP NKTCL group (P=0.006). Additionally, the CR rate after primary radiotherapy was 63.4% and 62.7%, respectively (P=0.629). The NP NKTCL patients with stage Ⅰ and Ⅱ who accepted radiotherapy with or without chemotherapy had similar survival times with chemotherapy alone, showing the 5-year OS rates of 70.5% and 33.3% (P=0.238), as well as the 5-year PFS rates of 56.7% and 33.3%, respectively (P=0.431). Similar results were found in N-NP NKTCL group, the 5-year OS rates for patients with radiotherapy with or without chemotherapy and chemotherapy alone were 57.4% and 33.3% (P=0.246), while the 5-year PFS rates were 49.3% and 16.7% (P=0.177), respectively. Besides, the relapse pattern of NP NKTCL and N-NP NKTCL groups was also similar, mainly involving the distant extra-nodal organs followed by lymph nodes. Conclusion: The patients with N-NP NKTCL and NP NKTCL showed similar clinical and prognostic features, however, the initial response to chemotherapy was different.

Respiratory epithelial adenomatoid hamartoma: a poorly recognized entity with mast cell recruitment and frequently associated with nasal polyposis.

Respiratory epithelial adenomatoid hamartoma (REAH) is regarded as a rare tumor of the nasal cavity. The mechanisms driving the development of REAH are unknown, and its nature as a benign tumor, hamartoma, or reactive inflammatory process is still open to discussion. A total of 150 consecutive patients operated on for nasal polyposis (NP) were extensively checked for the diagnosis of REAH. The profile of REAH occurring in association with NP was compared with solitary REAH in a series of 19 cases. The possible role of tryptase-producing mast cells (MC) and of metalloproteinases MMP2 and MMP9 in REAH development was investigated by immunohistochemistry. REAH lesions were identified in 35% of patients who had surgery for NP (53/150). The distribution of the lesions suggested that REAH originated in the olfactory cleft. Solitary REAH occurred about 20 times less frequently than those observed in an NP context but shared the same microscopic characteristics. Tryptase-producing MCs were recruited at high density in REAH (135/10 hpf), compared with inflammatory polyps (45/10 hpf; P<0.00005) and hypertrophied turbinates (51/10 hpf; P<0.0005). REAH also showed constant MMP9 expression and to a lesser degree MMP2 expression in epithelial cells. If solitary REAH is a relatively rare lesion, we demonstrated that an exhaustive sampling allows the detection of a high proportion of NP-associated REAH, sharing the same clinical and histologic characteristics with solitary REAH. Tryptase-producing MCs, possibly in association with MMP expression, may play a central role in REAH formation.

COX-2 expression and outcome in canine nasal carcinomas treated with hypofractionated radiotherapy.

The expression of cyclooxygenase isoform 2 (COX-2) in canine nasal carcinomas has been well documented. COX-2 expression has proven to be a prognostic factor in several human tumours. The aims of this study were to assess the correlation between immunohistochemical COX-2 expression and prognosis using rhinoscopic biopsies from 42 dogs with nasal carcinomas treated with hypofractionated radiotherapy, and to establish a replicable COX-2 scoring system. Ninety per cent of sections evaluated were COX-2 positive with a mean score of 6.6 (median 8.0; range 0-12). Neither COX-2 expression nor tumour type had a significant correlation with survival. There are likely to be many as yet unidentified variants which contribute to length of survival in dogs with nasal carcinomas. Immunohistochemical COX-2 expression appears unlikely to be of prognostic significance for canine nasal carcinoma.

Ganglioglioma in the nasal cavity: a case report.

Ganglioglioma is a tumor containing both astrocytic and neuronal components. It may occur any where in the central nervous system and spinal cord but is only encountered rarely. Nasal glial heterotopia (also known as ''nasal glioma''), is a rare developmental abnormality seen in a wide age group. Gangliogliomas may also manifest as a nasal glial heterotopia, and neurogenic tumors should be considered in the presence of a nasal mass. In this article, we present a case of ganglioglioma located in the right-nasal cavity. The mass was excised totally through an endoscopic approach. The ganglioglioma developed on a nasal glial heterotopia base. To our knowledge, a ganglioglioma arising from the nasal cavity has not been described previously in the literature.

Human topoisomerase II-alpha is highly expressed in sinonasal-inverted papilloma, but not in inflammatory polyp.

Sinonasal-inverted papilloma is a benign tumour with a high rate of recurrence, but possible malignant transformation. Therefore, investigation of predisposition to malignant transformation of sinonasal-inverted papilloma gives clinicians the opportunity for adequate treatment. Topoisomerase II-alpha (topoII-alpha) and Ki67 are markers of cell proliferation in both normal and neoplastic tissues and its level o expression could be used as a predictive parameter. Our goal was to investigate by immunochemistry the expression level of topoII-in inverted papilloma, inflammatory nasal polyp and normal sinonasal epithelium and to compare it with expression level of Ki67. TopoI alpha nuclear immunostaining showed a differential positivity in the investigated cases. The topoII-alpha index was 30.6 +/- 12.8 in inverte papilloma, 10.7 +/- 6.6 in the adjacent epithelium of inverted papilloma, but only 2.3 +/- 2.0 in the normal sinonasal epithelium. The differences in topoII-alpha expression between inverted papilloma and normal sinonasal epithelia were statistically significant. In inflammatory nasal polyp group, topoII-alpha index was 2.4 +/- 2.1, and the difference in the topoII-alpha index between inverted papilloma and inflammatory polyp group was also statistically significant. Nuclear immunostaining for Ki67 followed a similar variation. The Ki67 index was 50.0 +/- 20. in inverted papilloma, 9.0 +/- 6.6 in the adjacent epithelium of inverted papilloma and 2.4 +/- 0.9 in normal sinonasal epithelium. The differences in Ki67 expression between inverted papilloma and either adjacent or normal sinonasal epithelia were statistically significant. Significant correlation coefficients were found between topoII-alpha and epithelial thickness (r = 0.70, P > 0.0001), and between Ki67 index and epithelial thickness (r = 0.71, P> 0.0001). In the inflammatory nasal polyp group Ki67 index was 5.9 +/- 3.4. The difference in th Ki67 index between inverted papilloma and inflammatory nasal polyp groups was statistically significant. Significant correlation coefficient was found between topoII-alpha index and Ki67 index in inverted papilloma (r = 0.42, P > 0.05). These results suggest that the inverte papilloma contains a significantly higher cell population with proliferative activity by comparison with normal sinonasal and inflammatory polyp epithelia, showing a significant correlation between topoII-alpha and Ki67 expression, and indicating that topoII-alpha could be a independent prognostic factor for a putative malignant transformation.

Expression of cyclooxygenase-2 in canine nasal carcinomas.

Cyclooxygenase(COX)-2 expression was evaluated in 24 paraffin-embedded canine nasal carcinoma tissue samples by immunohistochemistry. Several different tumor types were represented, including carcinomas, adenocarcinomas and squamous cell carcinomas. COX-2 expression was identified in 17/24 cases (71%). The proportion of positive cells expressing COX-2 ranged from 10 to 95% and COX-2 expression was predominantly localized in the cytoplasm. Treatment with a COX-2 inhibitor should be investigated, along with the utilization of COX-2 expression as a prognostic marker.

Metalloproteinases in juvenile angiofibroma--a collagen rich tumor.

Matrix metalloproteinases (MMPs) act in diverse physiological and pathological conditions such as tumor growth and angiogenesis by cleaving extracellular matrix and nonmatrix substrates. MMPs with gelatinase/collagenase activity have not yet been studied in juvenile angiofibroma, a unique fibrovascular tumor with prominent collagen expression. Quantitative real-time polymerase chain reaction studies, Western blot analysis, immunofluorescence studies, gel zymography, and in situ zymography were used to analyze MMP-1, MMP-2, MMP-9, MMP-13, MMP-14, TIMP-1, and TIMP-2 in 9 juvenile angiofibromas and 2 inferior nasal turbinate specimens. Quantitative real-time polymerase chain reaction found significantly elevated expression of MMP-2, MMP-9, and MMP-14 (P < .05) in tumor tissue compared with the inferior nasal turbinate specimens. Western blot analysis detected more prominent MMP-1, MMP-2, and MMP-9 protein levels in juvenile angiofibromas compared with inferior nasal turbinates, but not MMP-13, MMP-14, TIMP-1, and TIMP-2. Immunofluorescent staining proved a mainly stromal localization of the analyzed MMPs. Only MMP-9 and MMP-14 were also detected in vessel walls. MMP-1, MMP-2, and MMP-13 also stained mast cells. Gel zymography indicated increased MMP-2 and MMP-9 gelatinase activity in juvenile angiofibromas compared with inferior nasal turbinates. Finally, in situ zymography detected very high stromal gelatinase/collagenase activity. This study indicates significant expression of MMPs with gelatinase/collagenase activity in juvenile angiofibromas with evidence of a disturbed balance of MMPs to TIMPs toward enhanced MMP activity. These MMPs are assumed to be involved in tumor pathology with an influence on tumor growth and angiogenesis.

Esthesioneuroblastoma - a clinicopathologic study and role of DNA topoisomerase alpha.

Esthesioneuroblastoma (ENB) differs from adrenal neuroblastomas in its histopathologic and biologic characteristics. Hyams grading and Kadish staging have shown correlation with survival. Scant data are available on proliferation indices and prognosis. We retrospectively reviewed the clinicopathologic characteristics of ENB. Both Kadish and UCLA staging systems were used. Hyams grading was simplified into low and high grade. DNA topoisomerase II alpha labeling index (T2alpha LI) was obtained in 8 cases using immunohistochemistry. Of the 19 cases studied, 14 were males and 5 females. Age range was 2 to 62 years (average 27 years). The mass primarily involved the nose in 12 (63%) and paranasal sinuses in 7 cases (37%). Patients presented with nose block in 19 (100%), epistaxis in 10 (53%), proptosis in 9 (47%) and loss of vision in 6 cases (32%). Bony involvement was seen in 7 cases (37%), and intracranial spread in one case (5%). Thirteen (68%) were low-grade tumors and 6 were (32%) high-grade. There was no statistically significant difference between the low- and high-grade ENB in age (years) (p=0.2882), duration of symptoms (months) (p=0.5636), and either in the Kadish (p=0.5456) or the UCLA staging system (p=0.7771). The difference in DNA topoisomerase alpha labeling index between the low- and highgrade ENB (medians: 10.4 and 22.3, respectively) was not statistically significant (p=0.0714), but it was suggestive of a positive association. The results of this study should be interpreted with caution, because of the limited sample size. Three cases recurred locally, one each stage A, B and C, but all low-grade. This preliminary study suggests the need to combine a simplified histologic grading with accurate staging in a reasonable attempt to assess local progression in esthesioneuroblastoma. Larger studies may clarify the role of T2alpha LI in improving histologic grading.

Prognostic factors for classifying extranodal NK/T cell lymphoma, nasal type, as lymphoid neoplasia.

This study evaluated the applicability of prognostic factors commonly used for diagnosis of classical lymphoma outcomes to extranodal NK/T cell lymphoma, nasal type (NTCL). Clinical features and their associations with lactate dehydrogenase (LDH) were evaluated in 70 patients. RLDH was defined as the ratio of LDH to the upper normal limit. RLDH was associated with stage (I-II vs. III-IV), lymph node involvement (LNI), and International Prognostic Index score (<2 vs. > or =2). Poor performance status and advanced stage were common in patients with local tumor invasiveness (LTI). LDH level, classified into three levels (low, high, and very high) was associated with survival (P < 0.001). In multivariate analysis, the predictive values of LDH level, B symptom, performance status, and stage remained significant whereas those of LTI and LNI did not. Scoring was performed by weighting each factor with 0.5 or 1.0 according to its hazard ratio. Scores were classified into four groups. Groups with high scores were associated with unfavorable outcomes (P < 0.001). Current study suggests that prognostic factors for NHL may be useful to predict the outcome of NTCL but the model should take LDH level and the prognostic weight of each factor into account.

Granzyme B leakage-induced apoptosis is a crucial mechanism of cell death in nasal-type NK/T-cell lymphoma.

This study aims to investigate the role of granzyme B in the apoptosis of nasal-type NK/T-cell lymphoma. Twenty-four nasal-type NK/T-cell lymphomas were examined by TdT-mediated deoxyuridine triphosphate (dUTP)-biotin nick-end labeling (TUNEL) assay and immunohistochemical staining for active caspase 3, poly(ADP-ribose) polymerase (PARP-1/p85)/p85, and Bcl-2. In addition, HANK-1 and NKL cell lines were analyzed using Western blot analysis. Immunoprecipitation was performed to identify the binding of granzyme B and intrinsic serpin proteinase inhibitor 9 (PI-9). To localize granzyme B, immunogold labeling and immunofluorescence staining were performed. The expression level of granzyme B in tumor tissue was correlated with the apoptosis rate (P=0.015), degree of necrosis (P=0.002), and the levels of active caspase 3 (P=0.036) and poly ADP-ribose polymerase (PARP)-1/p85 (P=0.040). The granzyme B-positive HANK-1 cell line showed increased spontaneous cell death compared to the granzyme B-negative NKL cell line. The untreated HANK-1 cells released cytochrome c into the cytosol with cleavage of caspase 3 and PARP-1. Treatment with granzyme B inhibitor and caspase inhibitor decreased the cleavage of PARP-1. By performing immunogold labeling, granzyme B was identified within the cytolytic granules as well as in the cytosol. Confocal microscopy and immunoprecipitation assays confirmed the colocalization of PI-9 and granzyme B, which formed an SDS-resistant complex. These results suggested that granzyme B leakage induces cell death in NK/T-cell lymphomas via both caspase-dependent and -independent mechanisms, and this leads to the extensive necrosis that is commonly seen in NK/T-cell lymphoma.

Activity of matrix metalloproteinase-2 (MMP-2) in canine oronasal tumors.

Activity of matrix metalloprotease-2 (MMP-2) and the expression of its related molecules were examined in spontaneous canine oronasal tumors. Tissue samples from melanoma and squamous cell carcinoma possessed higher MMP-2 activity, as shown in gelatin zymography, in comparison with acanthomatous epulis and nasal adenocarcinoma. Regional lymph node invasion and distant metastases were more frequently observed in the MMP-2 positive cases. There were no significant differences by RT-PCR examination in the expression of the genes encoding MMP-2, MT1-MMP and TIMP-2 among the tumor histological types. However, the MMP-2/TIMP-2 ratio showed a significantly higher level of the genes in the malignant oral melanoma and squamous cell carcinoma. The MMP-2/TIMP-2 ratio was also positively correlated with MMP-2 activity in gelatin zymography. These results indicate that the MMP-2/TIMP-2 ratio may be of value in evaluating the prognosis in canine oronasal cavity tumors.

In-situ demonstration of mitogen-activated protein kinase Erk 1/2 signalling pathway in contagious respiratory tumours of sheep and goats.

Ovine pulmonary adenocarcinoma (OPA) and enzootic nasal adenocarcinoma (ENA) are two contagious neoplastic diseases of secretory epithelial cells in the respiratory system of sheep and goats. Jaagsiekte sheep retrovirus (JSRV) is the aetiological agent of OPA, and enzootic nasal tumour virus (ENTV) is associated with ENA. The genomes of these retroviruses do not contain known oncogenes but products of the env gene are important in the generation of transforming stimuli. However, the cell signalling pathways activated in vivo are not completely understood. This study was based on the use of activation stage antibodies specifically detecting proteins of the extracellular signal regulated kinase Erk 1/2 cell signalling pathway and transcription factors. Tissue sections were collected from four natural cases of OPA, four experimentally induced OPA tumours, four ENA tumours in sheep, four ENA tumours in goats, two normal sheep lungs and two lungs with chronic inflammation. Routine immunohistochemical procedures with phosphorylation stage-specific antibodies were carried out. Representative proteins of the Erk1/2 pathway (Raf-1, Mek1/2 and p44/42MAPK) were activated in natural cases of OPA and ENA in sheep and goats and also in experimentally induced OPA. Transcription factors 90Rsk and Elk-1 were activated in OPA and ENA tumours. However, c-Myc was activated only in OPA tumours. In contagious respiratory neoplasms of sheep and goats the Erk1/2 pathway appears to be important for the in-vivo generation of the transforming stimuli.

[Metalloproteinase (MMP-1, 2 and 11), tissue inhibitor of metalloproteinase-1 (TIMP-1), and p53 expression in nasal-type angiocentric T/NK-cell lymphoma: an immunohistochemical study]. / Expresión inmunohistoquímica de metaloproteasas (MMP-1, 2 Y 11) e inhibidor de metaloproteasas de tejido-1 (TIMP-1), y expresión de p53 en linfomas angiocéntricos de células T/NK tipo nasal.

UNLABELLED: Twenty cases of extraganglionar Nasal-type T/NK-cell lymphomas were analyzed at the National Cancer Institute of Mexico. We studied immunophenotype of neoplastic cells, nuclear p53 expression, and enzymes as matrix metalloplroteinases participating in invasion, tissular destruction and metastases. MATERIAL AND METHODS: Paraffin blocks from all cases were retrieved and analyzed by hermatoxilin and eosin. Histopathological features included cellular size and cytologic characteristics. We performed immunohistochemistry to determine CD3, CD56, p53 cellular type and expression of (MMPs-1, 2, 11) matrix metalloproteinases and one tissue inhibitor of TIMP-1 metalloproteinase. Demographic variables included, age, sex, primaony location, clinical stage, treatment and follow-up. STATISTIC ALANALYSIS: The association of different matrix metalloproteinases in epthial and tumoral cells, stroma, necrosis and endothelial cells were found to be significant using Fisher's exact test. RESULTS: All studied cases were positive to cytoplasmic CD3, CD56 (NK cells), 19 of them were positive to p53, five of them with nuclear overexpression of p53 in more than 50% of neoplastic cells. There was significant expression of MMP-1 in tumoral cells; the epithelium displayed significant expression of TIMP-1 and MMP-11. Patients with p53 overexpression displayed a poorer prognosis. Three of them had undergone radiotherapy and died within the first month of treatment. DISCUSSION: This type of lymphoma is a common neoplasm in Asia, Latin America and Mexico. It is worth noting it has has been linked to Epstein-Barr virus with T/NK-cell phenotype, which often displays cellular atypia, an angiocentric growth pattern and necrosis. It is clinically expressed by progressive destruction of midline facial soft tissue and has a poor prognosis.

Expresión inmunohistoquímica de metaloproteasas (MMP-1, 2 y 11) e inhibidor de metaloproteasas de tejido-1 (TIMP-1), y expresión de p53 en linfomas angiocéntricos de células T/NK tipo nasal / Metalloproteinase (MMP-1, 2 and 11), tissue inhibitor of metalloproteinase-1 (TIMP-1), and p53 expression in nasal-type angiocentric T/NK-cell lymphoma. An immunohistochemical study

Se analizan 20 casos de linfomas extraganglionares de células T/NK de tipo nasal, estudiados en el Instituto Nacional de Cancerología, México, D. F., para su expresión inmunohistoquímica de las células neoplásicas, expresión nuclear de la proteína supresora de tumor p53, así como de enzimas que participan en invasión, destrucción tisular y metástasis: metaloproteasas. Material y métodos: Se estudió el material quirúrgico de estos casos y se efectuó tinción con hematoxilina y eosina analizando sus características histopatológicas: tamaño celular y detalle citológico. Se realizó estudio de inmunohistoquímica para corroborar el tipo celular, así como CD3 (células T), CD56 (células NK), expresión nuclear de la proteína supresora de tumor p53, y la expresión de metaloproteasas tipo 1, 2, 11 (MMP-1, 2, 11) y un inhibidor de metaloproteasas 1 (TIMP-1). Se analizaron variables demográficas, como edad del paciente, sexo, localización del tumor primario, etapa clínica, tratamiento en general y seguimiento. Estudio estadístico: Se analizó la prueba exacta de Fisher para correlacionar la expresión entre las metaloproteasas y su diferencial entre las células epiteliales, tumorales, estromales, necrosis y células endoteliales. Resultados: Los 20 casos fueron positivos CD3 citoplásmico, CD56, 19 de ellos positivos a p53, cinco de ellos con positividad nuclear mayor al 50% de las células neoplásicas. Hubo una mayor expresión citoplásmica tumoral de MMP-1; mayor expresión citoplásmica en el epitelio de TIMP1 y MMP-11. Los pacientes con sobreexpresión de p53 tuvieron un curso clínico fatal. Tres de ellos recibieron únicamente radioterapia falleciendo dentro del primer mes del tratamiento. Discusión: Los linfomas angiocéntricos de células T/NK tipo nasal son neoplasias frecuentes en los países de Asia, Latinoamérica, incluyendo a México. Frecuentemente esta patología se asocia a VEB con expresión fenotípica de células T/NK, cuyas características histológicas son: atipia celular linfoide, angioinvasión y necrosis, reflejado en los pacientes con destrucción progresiva de los tejidos blandos del macizo facial y curso clínico fatal.

Twenty cases of extraganglionar Nasal type T/NK cell lymphomas were analyzed at the National Cancer Institute of Mexico. We studied immunophenotype of neoplastic cells, nuclear p53 expression, and enzymes as matrix metalloproteinases participating in invasion, tissular destruction and metastases. Material and Methods: Paraffin blocks from all cases were retrieved and analyzed by hematoxilin and eosin. Histopathological features included cellular size and cytologic characteristics. We performed immunohisto chemistry to determine CD3, CD56, p53 cellular type and expression of (MMPs-1, 2,11) matrix metalloproteinases and one tissue inhibitor of TIMP 1 metalloproteinase. Demographic variables included, age, sex, primary location, clinical stage, treatment and follow up. Statistical analysis: The association of different matrix metalloproteinases in epithelial and tumoral cells, stroma, necrosis and endothelial cells were found to be significant using Fisher s exact test. Results: All studied cases were positive to cytoplasmic CD3, CD56 (NK cells), 19 of them were positive to p53, five of them with nuclear overexpression of p53 in more than 50% of neoplastic cells. There was significant expression of MMP-1 in tumoral cells; the epithelium displayed significant expression of TIMP 1 and MMP-11. Patients with p53 overexpression displayed a poorer prognosis. Three of them had undergone radiotherapy and died within the first month of treatment. Discussion: This type of lymphoma is a common neoplasm in Asia, Latin America and Mexico. It is worth noting it has has been linked to Epstein Barr virus with T/NK-cell phenotype, which often displays cellular atypia, an angiocentric growth pattern and necrosis. It is clinically expressed by progressive destruction of midline facial soft tissue and has a poor prognosis.

AKT plays a role in the survival of the tumor cells of extranodal NK/T-cell lymphoma, nasal type.

Phosphorylated AKT has been detected in extranodal NK/T-cell lymphoma, nasal type (ENTL). Either interleukin-2 (IL-2) or interleukin-15 (IL-15) could prevent AKT dephosphorylation and apoptosis in the NK-92 cell line model. IL-15, but not IL-2, was preferentially elevated in patients' serum. AKT and IL-15 may be important in ENTL tumor survival.

Expression of cyclooxygenase-2 in canine epithelial nasal tumors.

Cyclooxygenase-2 (COX-2) is an enzyme upregulated in some human and animal tumors. Enzymatic products are associated with tumorigenic activities. Given the poor response of canine nasal tumors to radiation, we considered the possibility that some of this resistance may be associated with COX-2 expression. To test this, 21 formalin-fixed, paraffin-embedded, and archived biopsy samples from canine epithelial nasal tumors were analyzed for COX-2 expression using immunohistochemistry. The biopsies were collected from dogs prior to radiation therapy. COX-2 expression was present in 17 of 21 (81%) tumors. The expression was observed in several different tumor types, including nasal carcinomas, adenocarcinomas, and squamous cell carcinomas. Samples from five control dogs without nasal neoplasia were also analyzed for COX-2 staining. These specimens were characterized by varying degrees of lymphoplasmacytic rhinitis with scattered regions of COX-2 positive respiratory epithelial and stromal cells. Whether the intensity and distribution of COX-2 expression in nasal tumors can be used as a prognostic marker requires further investigation. A combination therapy of irradiation and a selective COX-2 inhibitor appears worthy of clinical investigation in the treatment of canine epithelial nasal tumors.

Expression of cyclooxygenase-1 and -2 in canine nasal carcinomas.

Cyclooxygenase-1 (COX-1) and cyclooxygenase -2 (COX-2) are known to play a role in the carcinogenesis of many human and animal primary epithelial tumours. However, expression of COX-1 and -2 has not been investigated in canine nasal epithelial carcinoma, a rare form of neoplasia. COX-1 immunolabelling was demonstrated in normal canine nasal mucosa and in a minority of neoplastic specimens. Cytoplasmic COX-2, however, was strongly expressed in the majority of canine nasal carcinomas. In addition, COX-2 expression was demonstrated in dysplastic epithelium and in a proportion of stromal cells. Co-expression of both enzyme isoforms was revealed by confocal laser scanning microscopy. The results indicate that COX-2 is overexpressed in a proportion of naturally occurring canine nasal carcinomas, suggesting its possible role in canine nasal tumorigenesis.

The serine protease granzyme M is preferentially expressed in NK-cell, gamma delta T-cell, and intestinal T-cell lymphomas: evidence of origin from lymphocytes involved in innate immunity.

Granzyme M (GM) is a novel serine protease whose expression is highly restricted to natural killer (NK) cells, CD3(+)CD56(+) T cells, and gamma delta T cells. Using a GM-specific monoclonal antibody, we analyzed the expression of GM in 214 mature T-cell and NK-cell lymphomas. GM was preferentially expressed in nasal NK/T-cell lymphomas (100%), gamma delta T-cell lymphomas (100%), and intestinal T-cell lymphomas (85%). In contrast, GM expression was present at low prevalence in mycosis fungoides/Sézary syndrome (3%), anaplastic large-cell lymphoma (6%), panniculitis-like T-cell lymphoma (11%), and angioimmunoblastic T-cell lymphoma (0%) cases. Peripheral T-cell lymphomas of unspecified subtype showed an intermediate frequency (37%) of GM expression, consistent with their heterogeneous origin. We conclude that GM expression is a distinctive feature of the nasal NK/T-cell, gamma delta T-cell, and intestinal T-cell lymphomas, and suggest that these tumors develop from lymphocytes involved in innate immunity.