Lysyl-tRNA synthetase (KRS) expression in gastric carcinoma and tumor-associated inflammation.

BACKGROUND: Lysyl-tRNA synthetase (KRS) is an aminoacyl-tRNA synthetase (ARS) that is essential for protein synthesis during ligation of specific amino acids to their cognate tRNAs. Aberrant expression of ARSs is associated with various human cancers. METHODS: Using immunohistochemical detection, the present study analyzed the clinical relevance of KRS expression in tumor cells and tumor-associated inflammatory cells (TAI) in 457 patients who underwent curative radical surgery and standard adjuvant therapy and who were observed on long-term follow-up. RESULTS: High expression of KRS in tumor cells (tumor-KRS(+)) was noted in 43.3 % (198 of 457) of cases. High expression of KRS in tumor-associated inflammatory cells (TAI-KRS(+)) including macrophages/monocytes, CD4-positive T cells, and/or neutrophils was observed in 37.2 % (170 of 457) of cases. Status of KRS in the tumor and TAI revealed an association with the known clinicopathological parameters for prognosis of gastric cancer. Tumor-KRS(+) status correlated to shorter overall survival, especially in stage III to IV cancers (P = 0.003), while TAI-KRS(+) status correlated significantly to longer overall survival in gastric cancer (P = 0.049). Cases with tumor-KRS(+) and TAI-KRS(-) status showed significantly reduced survival rates compared to those of other cases (P = 0.010), and status of tumor-KRS(+) and TAI-KRS(-) was revealed as an independently poor prognostic factor of overall survival (P = 0.001). CONCLUSIONS: KRS-related inflammation can be identified in a subset of gastric cancer. This may be a possible mechanism of immune surveillance against tumor progression. In addition, expression status of KRS in tumor and TAI may be an independent prognostic marker for gastric cancer patients.

The diagnostic approach to fine-needle aspiration of malignant lymphoma: using cytomorphology and immunocytochemistry with cell transfer method.

Fine-needle aspiration (FNA) cytology is generally considered to be the screening tool for lymphoproliferative lesions. The differential and decisive diagnosis, however, of malignant lymphoma from benign reactive hyperplasia by FNA cytology is sometimes challenging. The diagnostic features compatible with lymphoma as opposed to reactive hyperplasia in FNA cytology were investigated with 31 cases of lymphoma and 31 cases of reactive hyperplasia, and immunocytochemistry with cell transfer method was additionally applied to FNA cytology. The predominance of large lymphocytes, the clustering of large lymphocytes, the presence of markedly large and/or highly pleomorphic cells, the presence of apoptotic and/or necrotic cell debris were considered characteristics of lymphomas, whereas the predominance of small lymphocytes and the presence of histiocytes were considered characteristics of reactive hyperplasia. Using these cytomorphologic characteristics, the diagnostic accuracy for malignant lymphoma in FNA cytology had a sensitivity of 80.6% and a specificity of 100%. By cell transfer method, one of Papanicolaou-stained slides could be used in immunocytochemistry for several markers. Using such methods, sensitivity of FNA cytology for lymphoma was upgraded to 100%, and decisive diagnoses of diffuse large B-cell lymphoma, Burkitt lymphoma, low grade B-cell lymphoma, T- or NK-cell non-Hodgkin lymphoma (NHL), or Hodgkin lymphoma was possible. Differential diagnosis of malignant lymphoma from reactive hyperplasia, and decisive diagnoses of high, and low grade B-cell NHL, T- or NK-cell NHL, and HL could be possible by FNA cytology with cytomorphology in conjunction with immunocytochemistry using cell transfer method.

Usefulness of Ki-67 (MIB-1) immunostaining in the diagnosis of pulmonary sclerosing hemangiomas.

Pulmonary sclerosing hemangioma (PSH) is an uncommon lung neoplasm with a clinical outcome that is generally benign. However, differentiating PSH from pulmonary carcinoma is sometimes difficult as both lesions share similar histopathologic and immunohistochemical features. In this study, we investigated the usefulness of Ki-67 (MIB-1) immunostaining in the diagnosis of PSH. We compared the staining pattern for Ki-67 (MIB-1) in 29 cases of typical PSH and 79 cases of pulmonary non-small cell carcinoma (NSCLC) using an immunohistochemical method on formalin-fixed paraffin-embedded tissues. In all studied PSH cases, we noted cell membrane and cytoplasmic staining for Ki-67 (MIB-1), but this was not observed in any of the NSCLC cases. The Ki-67 proliferation index was lower in PSH than in the NSCLC cases (mean, 1.1% vs mean, 5.5%; p < 0.001). These findings suggest that cell membrane and cytoplasmic staining for Ki-67 (MIB-1), as well as the Ki-67 proliferation index, may be useful for distinguishing PSH from pulmonary carcinoma.

Impact of grade, hormone receptor, and HER-2 status in women with breast cancer on response to specific chemotherapeutic agents by in vitro adenosine triphosphate-based chemotherapy response assay.

This study was designed to assess whether histological and biological factors of breast cancer can predict chemoresponse to specific agents. Adenosine triphosphate-based chemotherapy response assay (ATP-CRA) was employed to retrieve chemoresponse to 5-fluorouracil (5-FU), doxetaxel, doxorubicin, epirubicin, and paclitaxel in 49 patients. Tumors with high histologic and nuclear grade have higher response rate to doxorubicin (P<0.05) and palitaxel (P<0.05). Estrogen receptor (ER)-negative tumors respond well to doxorubicin (P=0.038), and progesterone receptor (PR)-negative tumors to 5-FU (P=0.039), doxetaxel (P=0.038), doxorubicin (P=0.000), epirubicin (P=0.010), and paclitaxel (P=0.003). Among the breast cancer subtypes determined by ER, PR, and HER-2 immunohistochemical stains, the HER-2+/ER- subtype has a higher response rate to doxorubicin (P=0.008). This in vitro result suggests that the combination of histologic and nuclear grade, hormone receptor, and HER-2 status can be a predictive factor of response to specific chemotherapy agents. Further in vivo study should be followed for clinical trials.