Soo Youn Cho

Role of adjuvant chemotherapy in malignant mucosal melanoma of the head and neck.

The objective of this study was to analyze the role of adjuvant chemotherapy and prognostic factors in malignant mucosal melanoma of the head and neck (HNMM). Thirty-two patients with mucosal melanoma of the head and neck who received local treatment with or without adjuvant chemotherapy were reviewed. Clinicopathologic parameters including anatomic sites, gender, age (60 vs.>60years), stage, level of invasion, p53 and MDM2 [murine double minute 2] expressions, performance status, and adjuvant chemotherapy were evaluated. The patients median age was 62years, and 16 (50%) received adjuvant chemotherapy. Expressions of p53 and MDM2 were demonstrated in six of 24 and three of 26 cases, respectively. Predictors of poor survival according to univariate analysis were level of invasion and anatomic location of the primary tumor. Patients who received adjuvant chemotherapy had prolonged survival (p=0.002), which was also shown in the multivariate Cox regression model (HR, 0.24; p=0.014). Our analysis suggests a significant role of adjuvant chemotherapy and different patterns of p53 and MDM2 expression in HNMM relative to cutaneous melanomas. However, since this study is retrospective and observational, with a small sample size, further studies are needed to confirm the definitive role of adjuvant chemotherapy in the treatment of malignant mucosal melanoma of the head and neck.

Central lymph node metastasis in papillary thyroid microcarcinoma can be stratified according to the number, the size of metastatic foci, and the presence of desmoplasia.

BACKGROUNDnLymph node (LN) metastasis is common in papillary thyroid microcarcinoma (PTMC). The aim of this study was to investigate the impact of LN metastasis and its risk stratification on PTMC recurrence.nnnMETHODSnWe retrospectively reviewed the data of 336 patients with PTMC who underwent surgery from 2005 to 2006 at a single institution. LN metastasis was stratified according to the number of metastatic LNs, the ratio of metastatic to removed LNs, the size of metastatic foci in LNs, and the presence of extranodal extension and desmoplasia.nnnRESULTSnOf the 336 patients, 93 (28%) had LN metastasis. During the follow-up of 5.3 years, 16 (4.8%) experienced locoregional recurrence. Among several clinicopathologic factors, LN metastasis was the most important risk factor for recurrence (P = .02). Lateral LN metastasis was correlated with recurrence-free survival (P < .01), whereas central LN metastasis was not (P = .20). When central LN metastasis was stratified, a high number of metastatic LNs (≥3), larger metastatic foci (≥0.2 cm), and the presence of desmoplasia were associated with recurrence-free survival (P < .05).nnnCONCLUSIONnThe prognostic significance of central LN metastasis can differ according to the number of metastatic LNs, the size of metastatic foci, and the presence of desmoplasia. Patients with a high number of metastatic LNs, larger metastatic foci, and presence of desmoplasia in LNs should be treated aggressively and supervised carefully for PTMC recurrence.

Predictive factors of malignancy in thyroid nodules with a cytological diagnosis of follicular neoplasm.

In cases of follicular neoplasm identified by thyroid fine-needle aspiration (FNA), surgery is required to achieve a precise diagnosis. We investigated potential clinical factors for the preoperative prediction of malignancy in thyroid nodules with a cytological diagnosis of follicular neoplasm. We retrospectively reviewed the data of 97 patients who were diagnosed with follicular neoplasm by FNA and had undergone surgery at the Korea Cancer Center Hospital between April 2010 and April 2012. Age, sex, laboratory data (such as thyroid-stimulating hormone, free T4, thyroglobulin (Tg), and Tg antibody), and ultrasonographic findings were reviewed from the electronic medical records. Of 97 patients, 50 (51.5xa0%) were diagnosed with benign nodules, 16 (16.5xa0%) with follicular thyroid carcinoma (FTC), and 31 (32.0xa0%) with papillary thyroid carcinoma (PTC). In comparison with the features of benign nodules, FTC presented with a large nodule size, high serum Tg level, isoechogenicity, calcifications, and peripheral halo, whereas PTC exhibited traits similar to those of benign nodules, except for high serum Tg level and the presence of calcifications on ultrasonography. Therefore, a high serum Tg level (≥75xa0ng/mL) and calcification were the only significant predictive factors for malignancy in case of follicular neoplasm (pu2009<u20090.01). Serum Tg levels and the presence of calcification on ultrasonography are important clinical features to predict malignancy in thyroid nodules with cytological diagnosis of follicular neoplasm.

Primary Gastric Choriocarcinoma: Two Case Reports and Review of the Literatures

Primary gastric choriocarcinoma (PGC) is a rare tumor, and its pathogenesis is still uncertain. Most PGCs have been reported to possess an adenocarcinoma component of variable extent, and pure PGC is especially rare. The diagnosis of PGC is confirmed by exhibition of choriocarcinomatous components on biopsy and exhibition of beta-hCG positive cell on immunohistochemical stain and elevation of the serum beta-hCG. Moreover it must be confirmed that no other site including gonads displays any tumor masses. The PGC tends to be more invasive and to have early metastasis. The median survival is known to be less than several months. We report two cases. The first case was a 62 year-old man who was diagnosed as advanced gastric cancer (AGC) by endoscopic biopsy with hepatic metastasis and received palliative chemotherapy with modified FOLFOX regimen and Genexol plus cisplatin regimen. He underwent subtotal gastrectomy due to perforation of the stomach during chemotherapy. On post-operative biopsy, He was re-diagnosed as PGC and received another palliative chemotherapy modified FOLFIRI, BEP, EMACO, VIP. However, multiple liver metastases were aggravated, and also serum AFP level increased. Ultimately, the patient died 10 months after initial diagnosis. Another case was a 45 year-old man. On endoscopic biopsy, he was diagnosed as AGC of adenocarcinoma. On Chest and Abdomen CT, multiple pulmonary and hepatic metastasis were also confirmed. On liver biopsy, He was diagnosed as PGC. The immunohistochemical stains were performed and the results were cytokeratin positive, EMA negative and beta-hCG weak positive. The serum beta-hCG level was highly elevated. BEP, VIP and EMA/CO combination therapy were administered, but he died at 12th months after the initial diagnosis.

Fine Needle Aspiration Cytology of Parathyroid Lesions

Background There has been an increase in the use of fine needle aspiration cytology (FNAC) for the diagnosis of parathyroid lesions (PLs). Differentiation between a thyroid lesion and a PL is not easy because of their similar features. We reviewed parathyroid aspirates in our institution and aimed to uncover trends in diagnostic criteria. Methods We selected 25 parathyroid aspirates (from 6 men and 19 women) confirmed surgically or immunohistochemically from 2006 to 2011. Results Major architectural findings of PLs include scattered naked nuclei, loose clusters, a papillary pattern with a fibrovascular core, tight clusters, and a follicular pattern. These architectures were commonly admixed with one another. Cytological features included anisokaryosis, stippled chromatin, a well-defined cell border, and oxyphilic cytoplasm. Eighteen of the 25 patients were diagnosed with PL using FNAC. Seven patients had been misdiagnosed with atypical cells (n=2), benign follicular cells (n=2), adenomatous goiter (n=2) and metastatic carcinoma (n=1) in FNAC. Using clinicoradiologic data, the sensitivity of the cytological diagnosis was 86.7%. The cytological sensitivity decreased to 50% without this information. Conclusions FNAC of PL is easily confused with thyroid lesions. A combination of cytological parameters and clinical data will be required to improve the diagnostic sensitivity of PLs.

High Expression of Aldo-Keto Reductase 1B10 Is an Independent Predictor of Favorable Prognosis in Patients with Hepatocellular Carcinoma

Background/Aims Upregulation of aldo-keto reductase 1B10 (AKR1B10) through the mitogenic activator protein-1 signaling pathway might promote hepatocarcinogenesis and tumor progression. The goal of this study was to evaluate the prognostic significance of AKR1B10 protein expression in patients with hepatocellular carcinoma after surgery. Methods A tissue microarray was used to detect the expression level of AKR1B10 protein in tumors from 255 patients with hepatocellular carcinoma who underwent curative hepatectomy. The impact of AKR1B10 expression on the survival of patients was analyzed. The median follow-up period was 119.8 months. Results High AKR1B10 protein expression was observed in 125 of the 255 patients with hepatocellular carcinoma (49.0%). High AKR1B10 expression was significantly associated with a lack of invasion of the major portal vein (p=0.022), a lack of intrahepatic metastasis (p=0.010), lower the American Joint Committee on Cancer T stage (p=0.016), lower the Barcelona Clinic Liver Cancer stage (p=0.006), and lower α-fetoprotein levels (p=0.020). High AKR1B10 expression was also correlated with a lack of early recurrence (p=0.022). Multivariate analyses of survival revealed that intrahepatic metastases and lower albumin levels were independent predictors of both shorter recurrence-free survival and shorter disease-specific survival. High AKR1B10 expression was an independent predictor of both longer recurrence-free survival (p=0.024) and longer disease-specific survival (p=0.046). Conclusions High AKR1B10 protein expression might be useful as a marker of a favorable prognosis in patients with hepatocellular carcinoma after curative hepatectomy.

High Expression of Ribonucleotide Reductase Subunit M2 Correlates with Poor Prognosis of Hepatocellular Carcinoma

Background/Aims Ribonucleotide reductase subunit M2 (RRM2) catalyzes the production of deoxynucleotide triphosphates, which are necessary for DNA synthesis. RRM2 has been reported to play an active role in tumor progression, and elevated RRM2 levels have been correlated with poor prognosis for colorectal cancer patients. This study aimed to elucidate the prognostic significance of RRM2 protein expression in hepatocellular carcinoma after surgery. Methods RRM2 protein expression was evaluated using immunohistochemistry in tumor tissues from 259 hepatocellular carcinoma patients who underwent curative hepatectomy. Results High RRM2 expression was observed in 210 of 259 patients (81.1%) with hepatocellular carcinomas. High RRM2 expression was significantly associated with viral etiology (p=0.035) and liver cirrhosis (p=0.036). High RRM2 expression was correlated with early recurrence (p=0.004) but not with late recurrence (p=0.144). Logistic regression analysis revealed that high RRM2 expression (p=0.040) and intrahepatic metastasis (p<0.001) were independent predictors of early recurrence. High RRM2 expression unfavorably influenced both shorter recurrence-free survival (p=0.011) and shorter disease-specific survival (p=0.002) and was an independent predictor of shorter disease-specific survival (p=0.008). Conclusions High RRM2 protein expression might be a useful marker for predicting early recurrence and may be a marker for poor prognosis of hepatocellular carcinoma after curative hepatectomy.

Expression of prothymosin α predicts early recurrence and poor prognosis of hepatocellular carcinoma

Background Prothymosin α (PTMA) is a nuclear oncoprotein-transcription factor essential for cell cycle progression and proliferation. PTMA was overexpressed in several human malignancies including hepatocellular carcinoma (HCC). However, the prognostic significance of PTMA protein expression in HCC remains unclear. In the present study, we evaluated PTMA protein expression by immunohistochemistry in order to elucidate the prognostic roles of PTMA in HCC patients. Methods By immunohistochemistry, we investigated the expression of PTMA protein in tumor tissue from 226 HCC patients who underwent curative hepatectomy. Univariate and multivariate analyses were performed to evaluate its predictive value for tumor recurrence and survival of patients. The median follow-up period was 120 months. Results PTMA expression was observed in 162 (71.7%) of the 226 HCC patients and was significantly associated with higher Edmondson grade, microvascular invasion, intrahepatic metastasis, higher American Joint Committee on Cancer (AJCC) T-stage, and lower albumin level. PTMA expression was an independent predictor of early recurrence (P=0.001). PTMA expression showed an unfavorable influence on recurrence-free survival (RFS) (P Conclusions PTMA protein expression might be a novel predictor of early recurrence and RFS in HCC patients, even those at early stage or with α-fetoprotein-negative after curative hepatectomy. PTMA could be used as an immunohistochemical biomarker to detect patients with a high risk of recurrence.

CD271 Confers an Invasive and Metastatic Phenotype of Head and Neck Squamous Cell Carcinoma Through the Upregulation of Slug

Purpose: Head and neck squamous cell carcinoma (HNSCC) is comprised of heterogeneous populations of cells, and CD271 (NGFR; p75NTR) has been associated with a tumor-initiating cell subpopulation. This study assessed the role of CD271 in modulating metastatic behavior in HNSCC. Experimental Design: CD271 was overexpressed in murine and human oral squamous cell carcinoma cells to assess the impact of CD271 activation on the invasive and metastatic phenotype of these cells, using in vitro and orthotopic in vivo modeling. Treatment with human nerve growth factor (NGF) to activate CD271, as well as shRNA knockdown of the CD271-upregulated Snai2 expression, was used to assess the mechanism of the CD271-induced invasive phenotype. Relevance of CD271 expression in human HNSCC was evaluated in patient-derived xenografts (PDX) and primary human oral cancers, annotated with clinical behavior characteristics and survival data. Results: Forced expression of CD271 resulted in a more invasive and metastatic phenotype. Slug, an epithelial-to-mesenchymal transition (EMT)-related transcription factor, encoded by Snai2, was highly expressed in MOC2-CD271 and HSC3-CD271, compared with respective parental cells. CD271 activation by NGF conferred enhanced invasiveness in CD271-overexpressing cells, which was abrogated by Snai2 knockdown. In PDXs and primary human HNSCC, CD271 expression correlated with higher Snai2 expression, greater nodal metastasis, and shorter disease-free survival. Conclusions: Activation of CD271 results in upregulation of Snai2/Slug, which, in turn, results in a more invasive phenotype and an enhanced capacity for metastasis to regional lymph nodes. These findings point to CD271 as a promising, therapeutic target for oral cancer metastasis. Clin Cancer Res; 24(3); 674–83. ©2017 AACR.

Invasive Paget disease of the breast: 20 years of experience at a single institution.

Mammary Paget disease with dermal invasion (invMPD) is rare, and its prognosis remains largely unknown. We reviewed MPD cases diagnosed at our institution and analyzed the clinicopathological characteristics of invMPD and non-invMPD to compare their incidences and outcomes. We retrospectively reviewed 205 cases of women diagnosed as having MPD between 1994 and 2013. Sixteen of 205 MPD cases (7.8%) had dermal invasion. Twelve of 16 invMPD cases had separate, underlying invasive breast carcinoma, and 3 invMPD cases had ductal carcinoma in situ. To exclude the influence of underlying disease on prognosis, we compared prognosis of invMPD with matched non-invMPD. The mean depth and extent of Paget cell invasion in invMPD cases were 0.637 and 1.268 mm, respectively. The horizontal extent of MPD was significantly larger in invMPD versus non-invMPD (mean, 14.31 mm versus 7.35 mm; P = .002). Distant metastasis and disease-related death were observed in 12.6% (24/189) and 12.1% (23/189) of non-invMPD patients, respectively, compared with 6.3% (1/16) and 6.3% (1/16) of invMPD patients; this difference was not significant (P = .7 and P = .7). Clinical outcomes of the invMPD patients were also not significantly different from the matched non-invMPD patients. In this study, MPD extent significantly correlated with MPD invasion. However, other clinicopathological parameters were not associated with dermal MPD invasion. Dermal MPD invasion was rare and did not predict regional lymph node metastasis or poor prognosis. The prognosis is usually similar for invMPD and non-invMPD, and MPD must be distinguished from locally advanced breast cancer presenting as satellite skin nodules.