Changyoung Yoo

Reduced expression of TFF1 and increased expression of TFF3 in gastric cancer: correlation with clinicopathological parameters and prognosis.

Objectives: The trefoil factor family (TFF) is composed of three thermostable, and protease-resistant proteins, named TFF1, TFF2 and TFF3, and plays a role in gastrointestinal mucosal defence and repair. Recently, TFFs have been found to be related to the development of various types of cancer. This study assessed the relationship between the expression of TFF1 and TFF3 and the clinicopathological parameters in gastric carcinoma (GC). Materials and Methods: The expression of TFF1 and TFF3 was analyzed by immunohistochemistry in 292 GCs and 20 normal gastric tissues. Results: All normal gastric tissues expressed TFF1, but 53.8% of GCs showed reduced TFF1 expression. However, TFF3 was not detected in normal gastric tissues and 44.2% of GCs showed a high level of expression. Highly expressed TFF3 was significantly correlated with lymph node metastasis, lymphatic invasion, vein invasion, and advanced stage. The overall survival was shorter in patients with high expression of TFF3 than in those with low expression of TFF3 in 292 GCs and in 125 early GCs (EGCs). Moreover, in patients with EGCs, high expression of TFF3, associated with reduced expression of TFF1, was determined as an independent poor prognostic marker. Conclusions: Reduced expression of TFF1 and increased expression of TFF3 may play a role in the carcinogenesis of gastric cancer. Furthermore, high expression of TFF3 with reduced expression of TFF1 may be a marker of poor prognosis for patients with EGC.

Hedgehog related protein expression in breast cancer: gli-2 is associated with poor overall survival.

Background The hedgehog (Hh) signaling pathway is known to play a critical role in various malignancies, but its clinicopathologic role in breast cancer is yet to be established. Methods Tissue microarray blocks from 334 cases of breast cancer were prepared. The expression of six Hh signaling proteins including sonic hedgehog (Shh), patched (Ptch), smoothened (Smo), and the glioma-associated oncogene (Gli)-1, Gli-2, and Gli-3 were analyzed immunohistochemically. Results The expression of Hh signaling proteins was significantly correlated with some prognostic factors including the correlation of lymph node metastasis with the expression of Shh (p=0.001) and Ptch (p=0.064), the correlation of the stages with Shh and Gli-3 expression (p=0.007 and p=0.024, respectively), the correlation of the nuclear grade with the Smo (p=0.004) and Gli-3 (p=0.000), and the correlation of the histologic grade with the Ptch (p=0.016), Smo (p=0.007), and Gli-3 (p=0.000). The Shh, Ptch, Smo, Gli-1, and Gli-2 expression was significantly different between the phenotypes (p=0.000, p=0.001, p=0.004, p=0.039, and p=0.031, respectively). Gli-2 expression was correlated with a worse overall survival outcome (p=0.012). Conclusions Hh pathway activation is correlated with a more aggressive clinical behavior in breast carcinomas. The comparison of phenotypes suggested that the Hh pathway may be a useful therapeutic target for breast carcinoma. Patients with Gli-2 expression had a significantly lower overall survival rate and, therefore, it showed promise as a prognostic marker.

A case of inflammatory myofibroblastic tumor originated from the greater omentum in young adult

Inflammatory myofibroblastic (IMF) tumor is a rare solid tumor that often affects children. IMF tumors occur primarily in the lung, but the tumor may affect any organ system with protean manifestations. A 22-year-old woman was evaluated for palpable low abdominal mass that had been increasing in size since two months prior. Abdominal computed tomography showed a lobulated, heterogeneous contrast enhancing soft tissue mass, 6.5 × 5.7 cm in size in the ileal mesentery. At surgery, the mass originated from the greater omentum laying in the pelvic cavity and was completely excised without tumor spillage. Histologically, the mass was a spindle cell lesion with severe atypism and some mitosis. Immunohistochemistry for anaplastic lymphoma kinase-1 revealed that the lesion was an IMF tumor. Because of its local invasiveness and its tendency to recur, this tumor can be confused with a soft tissue sarcoma. Increasing physician awareness of this entity should facilitate recognition of its clinical characteristics and laboratory findings.

Fine needle aspiration cytology of thyroid follicular neoplasm: cytohistologic correlation and accuracy.

Background This study evaluated the accuracy of fine needle aspiration cytology (FNAC) in cases of follicular neoplasm (FN) on the basis of histologic diagnosis, and reviewed the cytologic findings of FN according to the FNAC. Methods Among the 66 cases diagnosed with thyroid FN by FNAC during the 7-year period from 2003 to 2009, 36 cases that had undergone thyroid surgery were available for review. Cytologic diagnosis was compared with the histologic diagnosis of each case. Results Among the 36 cases with a cytologic diagnosis of thyroid FN, histologic diagnosis was as follows: 20 follicular adenomas (55.6%), 3 Hurthle cell adenomas (8.3%), 2 follicular carcinomas (5.6%), 8 nodular goiters (22.2%), 2 papillary carcinomas (5.6%), and 1 Hashimotos thyroiditis (2.8%), resulting in a diagnostic accuracy of FNAC for thyroid FN of 69.5%. Conclusions This study shows that FNAC for thyroid FN is a useful primary screening method because when FN is diagnosed by FNAC, the rate of FN histologic diagnosis is relatively high, however, adequate sampling and experience is a prerequisite for this procedure.

Review of atypical cytology of thyroid nodule according to the Bethesda system and its beneficial effect in the surgical treatment of papillary carcinoma

Purpose For the atypical cases of fine needle aspiration (FNA) cytology of thyroid nodules, ultrasonographic findings are a primary guideline for the surgical treatment. However, they have the intrinsic risk of overtreatment, as well. In this study we examined whether the Bethesda system could provide a real effect on the diagnostic rate of atypical cytology, and thereby reduce the number of cases diagnosed as atypical from FNA cytology. Methods We reviewed 166 cases diagnosed as atypical by FNA cytology at this institute between the years 2005 to 2010. We classified these cases on the basis of ultrasonographic and cytological findings and compared them with the histological results. Results Ultrasonographically, findings suspicious for malignancy and indeterminate were associated with 83.7% and 47.2% of malignancy rates, respectively. Cytopathologically, the malignancy rates varied according to the main cytological features and the highest malignancy rate was 77.3%. Based on the Bethesda system, 39.2% of the cases diagnosed as atypical could be grouped into the category of suspicious for malignancy and yielded a malignancy rate of 76.9%. Conclusion Although ultrasonography provides an excellent guideline for the surgical treatment of atypical cases, it also showed considerable risk of overtreatment. The Bethesda system did not offer definitive effects on the rate of atypical cytology, but this system seemed to provide stricter boundaries for the atypical cytology and to aid in reducing the rates thereof. This in turn may permit that more limited cases are allotted to ultrasonographic decision making.

Primary perivascular epithelioid cell tumor in the rectum: A case report and review of the literature

Perivascular epithelioid cell tumor (PEComa) is a rare collection of tumors arising in a wide array of anatomic locations. It is characterized by the presence of a peculiar population of myomelanocytic marker-positive perivascular epithelioid cells, and is commonly detected in the uterus. The colorectal area is an uncommon site for primary PEComa. In this study, we describe a 17-year-old patient presenting with a rectal polyp. Histologically, the tumor consisted of sheets of round to polygonal epithelioid cells with clear and granular cytoplasm, and a prominent capillary network. Some of the tumor cells were positive for Fontana-Masson staining. Immunohistochemically, the tumor cells were positive for HMB-45, and were negative for cytokeratin, vimentin, S-100 protein, actin, desmin, EMA, CD34, and c-kit. After finding melanosomes or premelanosomes at the ultrastructural level, the diagnosis of PEComa was made. Although PEComa arising within the intestinal tract is unusual and clinically unexpected, PEComa should be considered in the differential diagnosis of rectal polypoid lesions.

Expression of Histone Deacetylases in Diffuse Large B-cell Lymphoma and Its Clinical Significance

Background: Histone deacetylase inhibitors are a new class of drugs used in treatment of malignant tumors. Diffuse large B-cell lymphoma (DLBCL) is the most common type of B-cell lymphoma, and it accounts for more than 40% of all B-cell lymphomas. In this study, we aimed to determine the expression patterns of histone deacetylases (HDACs) in DLBCL, to examine whether HDAC expression patterns differ among cases, and to assess whether these findings have clinical significance. Materials and methods: We selected 91 cases of DLBCL diagnosed at St. Vincent Hospital, The Catholic University of Korea, from 2001-2012. We performed a pathology slide review and collected clinical data including age, sex, tumor site, survival time, and mortality. Immunohistochemical analysis was performed using primary antibodies for HDACs, including HDAC1 and 2 of class I, HDAC4 and 5 of class IIa, and HDAC6 of class IIb. Expression site was determined to be nuclear, cytoplasmic, or both. Staining intensities were graded as low and high. We assessed correlations between HDAC expression levels and clinical data and survival analysis. Results: Of the 91 cases examined, 46 (50.5%) were men and 45 (49.5%) were women. Most of the patients were elderly, and 74 (81.3%) cases were older than 46 y. Forty-six (50.5%) cases showed lymph node involvement, and 45 (49.5%) cases showed lymphoma at extranodal sites. In nodal lymphoma, staining was strongly positive for HDAC2, whereas staining was weak or negative for HDAC4; however, there was no significant correlation with survival. But nodal lymphoma cases with high nuclear expression of HDAC2 and nodal lymphoma cases with high nuclear expression of HDAC2 and low nuclear expression of HDAC4 showed significantly shorter survival times compared with other cases. Conclusions: High nuclear expression of HDAC2 may play an important role in survival of DLBCL patients, especially in those with nodal lymphoma, which is associated with a shorter survival time. Our results may have important implications for treatment of DLBCL by epigenetic regulation.

Microtubule-Associated Protein Tau, α-Tubulin and βIII-Tubulin Expression in Breast Cancer

Background The microtubule-associated protein Tau binds to both inner and outer surfaces of microtubules, leading to tubulin assembly and microtubule stabilization. The aim of this study was to evaluate the significance of Tau, α-tubulin, and βIII-tubulin expression in breast carcinoma and to assess their relationships with disease progression in the context of taxane treatment. Methods Immunohistochemical expressions of Tau, α-tubulin, and βIII-tubulin were assessed in 183 breast cancer cases. Expression was correlated with clinicopathologic parameters, disease progression and overall survival. Results Tau expression was correlated with lymph node metastasis and estrogen receptor (ER) positivity (p=.003 and p<.001, respectively). Loss of α-tubulin was significantly correlated with distant metastasis (p=.034). Loss of βIII-tubulin was correlated with lymph node metastasis and ER positivity (p=.004 and p<.001, respectively). In taxane-treated cases, Tau expression and loss of α-tubulin and βIII-tubulin expression were related to disease progression (p=.001, p=.028, and p=.030, respectively). Tau expression was associated with a worse survival rate in taxane-treated patients (p=.049). Conclusions Tau expression and loss of α-tubulin and βIII-tubulin expression were correlated with aggressive behavior in taxane-treated breast cancer. Further evaluation of Tau, α-tubulin and βIII-tubulin may be useful in predicting clinical behavior and seeking therapeutic measures in taxane-based chemotherapy for breast cancer.

Primary mesenteric carcinoid tumor

Primary mesenteric carcinoid tumor is very rare, although secondary mesenteric involvement is common, reported as 40% to 80%. And distant metastasis rate reported as 80% to 90%, when the size is larger than 2 cm. We present a case of very rare primary mesenteric carcinoid tumor showing benign character though large size. The patient visited St. Vincents Hospital, The Catholic University of Korea with increasing palpable abdominal mass. At laparotomy, a well encapsulated mass arising from the mesentery near the ligament of Treitz was found without any adjacent organ invasion or distant metastasis. The mass was measured as 8.2 × 7.3 cm and histopathologically benign character. At 11 months of follow up, the patient was recurrence free.

A Proposal for Creating a Guideline for Cancer Registration of the Fibromatosis, PEComa Group, Malignant Lymphoma In Situ and Dendritic Cell Tumors (III)

Background Understanding the biologic behavior of a tumor is a prerequisite for tumor registration code assignment. The aim of this report was to propose appropriate behavior codes of the International Classification of Disease Oncology 3 (ICD-O3) to rare, yet pathologically interesting hematopoietic and soft tissue tumors. Methods The Study Group for Hematopathology, the Bone and Soft Tissue Pathology Study Group, and the Cancer Registration Committee prepared the questionnaire containing provisional behavior codes of selected diseases. Results In situ lesions of mantle cell and follicular lymphomas, dendritic cell tumors, and neoplasms with perivascular epithelioid cell differentiation (PEComa), not otherwise specified were classified as malignant (-/3). The fibromatosis group, with the exception of lipofibromatosis, was proposed as benign (-/0). Lipofibromatosis and several diseases that belong to the PEComa group were proposed as uncertain malignant potential (-/1). For the hematologic and soft tissue tumors, 274 and 288 members of the Korean Society of Pathologists, respectively, provided opinions through questionnaire, and most responders showed agreement with the provisional behavior code proposed. Conclusions The determination of behavior codes for the rare diseases described in this study, especially those of the PEComa group or malignant lymphoma, could be viewed as impractical and premature, but this study provides the basis for future research on this topic.