Kyo Young Lee

Non-small cell lung cancers frequently express phosphorylated Akt; an immunohistochemical study

Mounting evidence suggests that the alterations of Akt/protein kinase B (PKB) play an important role in tumorigenesis. Phosphorylated Akt regulates many of the key effector molecules involved in apoptosis, angiogenesis, and cell cycle progression during tumorigenesis. The expression of phosphorylated Akt has been described in some human malignancies, but not in primary human lung cancer. In this study, to understand the role of Akt in lung tumorigenesis we analyzed the expression of phosphorylated Akt in 43 non‐small cell lung cancers (NSCLCs) by immunohistochemistry. Phosphorylated Akt was detected either in the cytoplasm (23 cases) or nucleus (6 cases) in 29 of 43 NSCLCs (67.4%). Squamous cell carcinomas, adenocarcinomas, and bronchioloalveolar carcinomas expressed phosphorylated Akt in 68.2%, 61.5% and 75%, respectively. We also analyzed the phosphorylated Akt expression between primary NSCLCs and their corresponding nodal metastasis; the expression was not, however, different between the primary and metastatic lesions. Taken together, these results indicate that Akt 1 is frequently activated in NSCLCs, irrespective of the histological subtypes, and suggest that phosphorylated Akt may play a role in the development of NSCLC rather than in the progression of NSCLC.

Alterations of Fas-pathway genes associated with nodal metastasis in non-small cell lung cancer.

Many types of cancer cells are resistant to Fas-mediated apoptosis by several mechanisms, including the mutations of the genes involved in Fas-mediated apoptosis. In this study, to explore the possibility that the mutations of the genes involved in the proximal pathway of Fas-mediated apoptosis (Fas, FADD, caspase 8 and caspase 10) are involved in cancer metastasis, we have analysed somatic mutation and deletion of these genes in 80 non-small cell lung cancers (NSCLCs) with (n=43) and without (n=37) metastasis to the regional lymph nodes. We found 12 mutations (four Fas, four FADD, and four caspase 10 mutations) in 11 of 80 NSCLCs (13.8%). Interestingly, of these mutations, most mutations (10 out of 12) were detected in the NSCLCs with metastasis, and the frequency in the metastasis lesions (23%) was higher than that in the primary lesions of the NSCLCs without metastasis (5.4%). Furthermore, transfection study revealed that the tumor-derived mutants have decreased apoptosis inductions compared to the wild types. These data suggest that the inactivating mutations of the genes in the proximal pathway of Fas-mediated apoptosis may lead to a decreased cancer cell death and play a role in the metastasis of NSCLC.

Expression of transforming acidic coiled-coil containing protein 3 is a novel independent prognostic marker in non-small cell lung cancer

Transforming acidic coiled‐coil containing protein 3 (TACC3) is known to be involved in the control of normal cell growth and differentiation and in mechanisms of unregulated growth leading to tumorigenesis. The aim of the present paper was to determine the rate of TACC3 expression in a non‐small cell lung cancer (NSCLC) collection and to clarify its correlation with clinicopathological parameters. A total of 163 NSCLC were analyzed immunohistochemically using a polyclonal TACC3 antibody and monoclonal p53 and Ki‐67 antibodies on NSCLC tissue microarrays. A high level of TACC3 expression was observed in 14.8% of cases, preferentially squamous cell carcinomas. Patients whose tumors had a high TACC3 expression had a significantly shorter median survival time. In the Cox regression‐based multivariate analysis, TACC3 expression proved to be an independent prognostic parameter (P = 0.031). TACC3 expression was correlated with p53 expression, and patient whose tumors highly expressed TACC3 and p53 had a significantly poorer prognosis than patients whose tumors had low‐level expression for both immunostainings (P = 0.006). It is suggested that increase in TACC3 may impart a proliferative advantage to NSCLC and contribute to tumor progression, and that TACC3 expression is a strong prognostic indicator of clinical outcome in NSCLC.

Benign tumors of the tracheobronchial tree: CT-pathologic correlation.

OBJECTIVE The purpose of this essay is to illustrate the CT findings of variable benign tumors of the tracheobronchial tree and to correlate the CT and pathologic findings in 17 patients. CONCLUSION The tracheal tumors were eccentric, well-defined, polypoid masses in all cases. The endobronchial tumors were masses confined within the bronchus in all cases, and atelectasis or pneumonia of the distal parenchyma was frequently associated. Of the six hamartomas, one was a fatty mass, and two were nodules with calcification. The others were soft-tissue-density nodules. The lipomas manifested as fat density on CT scans in both cases. The other benign tumors were low-attenuating, soft-tissue-density masses without characteristic findings on CT scans.

Emphysematous gastritis associated with invasive gastric mucormycosis: a case report.

Emphysematous gastritis is a rare form of phlegmonous gastritis, characterized by air in the wall of the stomach due to invasion by gas-forming microorganisms. The most commonly involved microorganisms are streptococci, Escherichia coli, Pseudomonas aeruginosa, Clostrodium perfrigens and Staphylococcus aureus. Gastrointestinal mucormycosis is another rare condition, which is most frequently occurs in the stomach. Because emphysematous gastritis associated with invasive gastric mucormycosis is an extremely rare clinical condition and both are life-threatening diseases, early precise diagnosis and early treatment should be done to avoid mortality. Herein we present an extremely rare case of emphysematous gastritis associated with invasive gastric mucormycosis. A 43-yr-old man, suffering from alcoholism and diabetes, has experienced diffuse abdominal pain for 4 days. Abdominal computed tomography scan demonstrated gas within the stomach wall. A histologic examination of the total gastrectomy specimen showed several gas-filled bubbles in the wall, along with numerous fungal hyphae throughout the necrotic stomach wall. He died of multiorgan failure secondary to disseminated mucormycosis, despite the intensive medical therapy.

Expression of Functional Markers in Acute Nonlymphoblastic Leukemia

Multidrug resistance parameters, tissue infiltration parameters, receptors for colony-stimulating factors (CSFr) and cell cycle parameters were analyzed using flow cytometry in 145, 109 initial and 36 relapsed or refractory, acute nonlymphoblastic leukemia (ANLL) patients to find out clinically more reliable functional parameters. Lung resistance-associated protein (LRP) was most frequently expressed in ANLL (44.1%) followed by P-glycoprotein (PGP) (35.9%) and multidrug resistance-associated protein (MRP) (8.3%). LRP and PGP were expressed more frequently in relapsed or refractory ANLL than initial ANLL cases. Complete remission rate after standard chemotherapy falls in PGP-positive cases (p = 0.001). CD44-positive ANLL cases relapsed more frequently. The organ tropism is different depending on the infiltration parameters, vascular cell adhesion molecule to splenomegaly, matrix metalloprotease-2 to hepatomegaly and to extramedullary infiltration other than spleen, liver or lymph node. The percentage of the granulocyte-macrophage-CSFr expression was high in M4 and M5, and granulocyte-CSFr-positive ANLL showed less extramedullary infiltration (p = 0.007) and more PGP expression. Ki-67 was expressed significantly less in refractory ANLL than initial ANLL and DNA topisomerase IIα was expressed significantly more in the surviving patients group. In conclusion, analysis of these new functional parameters could help to predict and overcome the clinical behavior of each ANLL at the time of diagnosis.

The use of an immunohistochemical diagnostic panel to determine the primary site of cervical lymph node metastases of occult squamous cell carcinoma.

Cervical lymph node metastases from unknown primary sites account for approximately 3% to 9% of all head and neck malignant lesions. Squamous cell carcinoma is the most common type of cervical metastatic carcinoma. Our aim was to investigate the possibility of determining the site of primary tumors using an immunohistochemical diagnostic panel in metastatic cervical lymph nodes. Expression profiles of cytokeratins, 5/6; 8/18; 10; 13; 14; and 19, p16, and pRb were evaluated in 101 consecutive patients with cervical nodal metastasis who had undergone neck dissection to treat known head and neck squamous cell carcinoma (primary sites: 16, oral cavity; 38, oropharynx; 26, hypopharynx; 21, larynx). Cytokeratin 10 was more frequently expressed in oral cavity primary tumors, whereas cytokeratin 19 staining was more frequently observed in tumors originated from the pharynx and larynx. The expression of p16 and altered pRb status (0% or >50%) were more frequently observed in oropharynx primary tumors. To select the best subset among the 8 antibodies tested, classification and regression tree analysis was performed. The analysis correctly classified the four primary sites (25.0% of oral cavity, 89.5% of oropharynx, 30.8% of hypopharynx, and 57.1% of larynx) using 5 variables (histologic subtype, p16, cytokeratins 10 and 19, and pRb). The p16 was the single best predictor. The classification tree method using immunostaining profiles of p16, cytokeratins 10 and 19, or pRb may be helpful in the identification of the primary site of metastatic squamous cell carcinoma with occult primary.

Increased Incidence of Colorectal Malignancies in Renal Transplant Recipients: A Case Control Study

This study was to evaluate the frequency of colorectal neoplasia in renal transplant recipients and to investigate the association with Epstein‐Barr virus (EBV) and cytomegalovirus (CMV) infection. We compared the frequency of colorectal neoplasia among renal transplant recipients with that of the healthy subjects. Specimens of colorectal neoplasia were examined for EBV and CMV using in situ hybridization and immunohistochemistry, respectively. Of 796 renal transplantation cohorts, 315 were enrolled. The frequency of colorectal neoplasia among the patients was 22.9%. Compared with the healthy subjects, the odds ratio (OR) for advanced adenoma was 3.32 (95% CI, 1.81–6.10). The frequency of cancer among the patients was 1.9% (OR, 12.0; 95% CI, 1.45–99.7). A long interval between transplantation and colonoscopy was a significant factor in the development of advanced colorectal neoplasia. EBV positivity was detected in 30.6% of colorectal neoplasia specimens from renal transplant recipients, which was higher than that for the controls (p = 0.002). CMV was not detected in any lesions of patients or controls. In conclusion, renal transplant recipients have a significantly increased risk of advanced colorectal neoplasia. EBV was more frequently found in specimens of advanced colorectal neoplasm obtained from the renal transplant recipients.

Teratoma with Malignant Transformation in the Anterior Mediastinum: A Case Report

Malignant transformation of teratoma in the anterior mediastinum is rare; the mass usually has a long history and is seen in older patients. We report a case of teratoma with malignant transformation in the anterior mediastinum, complicated by rupture. CT revealed a lobulated, inhomogeneous cystic mass with a fat component and wall calcifications. The lateral wall was disrupted and consolidation in the adjacent left upper lobe was noted, suggesting rupture. A heterogeneously enhanced solid portion, obliterating the fat plane between the mass and the great vessels was present in the medial aspect of the mass, and pathologic examination demonstrated the presence of adenocarcinoma.

Epstein-Barr virus infection, drug resistance and prognosis in Korean T- and NK-cell lymphomas.

T‐cell lymphomas are a biologically heterogeneous group of diseases with varying clinical presentations and outcomes. We tried to understand the effect of Epstein–Barr virus (EBV) on lymphogenesis, prognostic factors and drug resistance of T‐cell lymphomas, and to establish their relationship with international prognostic factors. Formalin‐fixed paraffin‐embedded tissue sections from 35 patients (12 women and 23 men) with T‐cell lymphomas were examined to detect the presence of EBV using RNA in situ hybridization for EBV‐encoded small nuclear RNA (EBER) 1/2 and immunohistochemical stain for latent membrane protein (LMP)‐1. We also tried to establish the expression of p53 and P‐glycoprotein (P‐gp) using immunohistochemistry. The distribution according to the subgroup was: two T‐lymphoblastic lymphomas, 13 NK/T‐cell lymphomas, one angioimmunoblastic T‐cell lymphoma, 17 peripheral T‐cell lymphomas, unspecified, and two anaplastic large cell lymphomas. The EBER was detected in 15 of 35 T‐cell lymphomas (42.9%) and among these it was detected in five of 17 nodal lymphomas (29.4%) and 10 of 18 extranodal lymphomas (55.6%). There was close correlation between EBER positivity and NK/T‐cell lymphoma (P= 0.032). Expression of LMP was found in a proportion of tumor cells in seven of the 15 EBER‐positive cases (46.7%). There was no correlation between EBER expression and complete response (CR rate), but coexpression of EBER and p53 was associated with treatment failure (P= 0.047). The 18 patients (51.4%) with p53 expression had significantly poorer outcomes compared with the 17 patients without p53 expression (CR rate, P< 0.0005; overall survival, P= 0.0102). Twenty of 35 patients (57.1%) were positive for P‐gp expression. P‐gp expression was significantly associated with treatment failure (P= 0.001) and overall survival (P= 0.0089). Seventeen of 35 patients (48.6%) treated with systemic chemotherapy or radiation therapy achieved a CR after initial treatment. When the prognostic factors were grouped using the international prognostic index, the CR rate was 58.8% for the low risk group, 50.0% for the low–intermediate risk group, 14.3% for the high–intermediate risk group, and 0% for the high risk group. In conclusion, high incidence of EBV was detected among Korean patients with T‐cell lymphomas. Our study supports the prediction that patients who express p53 and P‐gp have a poorer prognosis than those who do not and this should be considered when treatment strategies for individual patients are selected.