Prevalence of BRAFV600E Mutation in Follicular Variant of Papillary Thyroid Carcinoma and Non-Invasive Follicular Tumor with Papillary-Like Nuclear Features (NIFTP) in a BRAFV600E Prevalent Area.

BACKGROUND: BRAFV600E mutation status and prevalence of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) has not yet been reported in Korea. The aim of this study was to investigate the significance of the BRAFV600E mutation in the follicular variant of papillary thyroid carcinoma (FVPTC) and to determine the prevalence of NIFTP in BRAFV600E mutation-prevalent Korean patients. METHODS: This study retrospectively analyzed 1,417 consecutive patients who underwent total thyroidectomy with routine prophylactic central lymph node dissection for papillary thyroid carcinoma (PTC). BRAFV600E mutation analysis was performed routinely using multiplex polymerase chain reaction by applying dual priming oligonucleotide. Clinicopathological characteristics and ultrasonographic findings were compared between BRAFV600E mutation-positive and -negative groups for FVPTC. Pathologists reviewed the pathology slides according to consensus diagnostic criteria for the encapsulated FVPTC and NIFTP. RESULTS: The prevalence of the BRAFV600E mutation in all subtypes of PTC was 61.0% (861/1,411). FVPTC presented a BRAFV600E mutation rate of 27.3%. The FVPTC patients with BRAFV600E mutation were older than those with no BRAFV600E mutation (P = 0.021). The prevalence of NIFTP was 0.18% among all PTC patients (2/1,411) and the proportion of NIFTP among FVPTC was 9.1% (2/22). CONCLUSION: The BRAFV600E mutation is prevalent in Korean patients with FVPTC in a region with high frequency of the BRAFV600E mutation and very low prevalence of NIFTP compared with that reported in western studies.

Primary Glomerulonephritis with Unique C4d Deposition and Concurrent Non-infectious Intermediate Uveitis: a Case Report and Literature Review.

C4 glomerulopathy is a recently introduced entity that presents with bright C4d staining and minimal or absent immunoglobulin and C3 staining. We report a case of a 62-year-old man with C4 glomerulonephritis (GN) and uveitis. He presented to the nephrology department with proteinuria and hematuria. The patient also had intermediate uveitis along with proteinuria and hematuria. A kidney biopsy that was performed in light of continuing proteinuria and hematuria showed a focal proliferative, focal sclerotic glomerulopathy pattern on light microscopy, absent staining for immunoglobulin or C3 by immunofluorescence microscopy, with bright staining for C4d on immunohistochemistry, and electron-dense deposits on electron microscopy. Consequently, C4 GN was suggested as the pathologic diagnosis. Although laser microdissection and mass spectrometry for glomerular deposit and pathologic evaluation of the retinal tissue were not performed, this is the first report of C4 GN in Korea and the first case of coexisting C4 GN and uveitis in the English literature.

Pheochromocytoma as a rare cause of hypertension in a 46 X, i(X)(q10) turner syndrome: a case report and literature review.

BACKGROUND: Cardiovascular disease (CVD) presents the most serious health problems and contributes to the increased mortality in young women with Turner syndrome. Arterial hypertension in Turner syndrome patients is significantly more prevalent than that in a general age-matched control group. The aetiology of hypertension in Turner syndrome varies, even in the absence of cardiac anomalies and obvious structural renal abnormalities. Pheochromocytoma is an extremely rare cause among various etiologies for hypertension in patients with Turner syndrome. Here, we reported a pheochromocytoma as a rare cause of hypertension in Turner syndrome patient. CASE PRESENTATION: A 21-year-old woman who has diagnosed with Turner syndrome with a karyotype of 46,X,i(X)(q10) visited for hypertension and mild headache. Transthoracic echography (TTE) showed no definite persistent ductus arteriosus shunt flow and cardiac valve abnormalities. Considering other important secondary causes like pheochromocytoma, hormonal studies were performed and the results showed increased serum norepinephrine, serum normetanephrine, and 24 h urine norepinephrine. We performed an abdominal computed tomography (CT) to confirm the location of pheochromocytoma. Abdominal CT showed a 1.9 cm right adrenal mass. I-131 meta-iodobenzylguanidine (MIBG) scintigraphy showed a right adrenal uptake. Laparoscopic adrenalectomy was performed and confirmed a pheochromocytoma. After surgery, blood pressure was within normal ranges and postoperative course was uneventful, and no recurrence developed via biochemical tests and abdominal CT until 24 months. CONCLUSION: Our case and previous literatures suggest that hypertension caused by pheochromocytoma which is a rare but important and potentially lethal cause of hypertension in Turner syndrome. This case underlines the importance of early detection of pheochromocytoma in Turner syndrome. Clinicians should keep in mind that pheochromocytoma can be a cause of hypertension in patients with Turner syndrome.

Regenerative potential of tonsil mesenchymal stem cells on surgical cutaneous defect.

As tissue engineering and regenerative medicine have evolved recently, stem cell therapy has been investigated in the field of impaired wound healing. Several studies have reported that mesenchymal stem cells derived from various tissues including bone marrow and adipose tissue can exert the regenerative efficacy in the wound healing. Previously, we have demonstrated the isolation and characterization of tonsil-derived mesenchymal stem cells (TMSCs) with excellent proliferative property. In the present study, we aimed to evaluate the regenerative efficacy of TMSCs in the wound healing process. Two distinct cutaneous surgical defects were generated in the dorsum of mice. Each wound was treated with TMSCs or phosphate-buffered saline (PBS), respectively. After sacrifice, the skin and subcutaneous tissues around the surgical defect were harvested and assessed for inflammation, re-epithelialization, dermal regeneration, and granulation tissue formation. The administration of TMSCs into wound beds significantly promoted the repair of surgical defects in mice. Especially, TMSCs efficiently contributed to the attenuation of excessive inflammation in the surgical lesion, as well as the augmentation of epidermal and dermal regeneration. To elucidate the underlying mechanisms, TMSCs were analyzed for their potency in immunomodulatory ability on immune cells, stimulatory effect on the proliferation of keratinocytes, and fibroblasts, as well as the regulation of fibroblast differentiation. TMSCs inhibited the non-specific or T-cell-specific proliferation of peripheral blood mononuclear cells, as well as the M1 polarization of macrophage-like cells. Moreover, TMSCs augmented the proliferation of skin-constituting fibroblasts and keratinocytes while they suppressed the differentiation of fibroblasts into myofibroblasts. Taken together, our findings demonstrate the regenerative potential of TMSCs in wound healing process through the regulation on inflammation, proliferation, and remodeling of various skin cells, implying that TMSCs can be a promising alternative for wound repair.

The significance of tumor budding in T1 colorectal carcinoma: the most reliable predictor of lymph node metastasis especially in endoscopically resected T1 colorectal carcinoma.

Endoscopic resection is widely recognized as a first-line treatment for T1 colorectal cancers (CRC), although additional surgical intervention may be indicated based on the risk of lymph node (LN) metastasis. However, risk factors for LN metastasis in T1 CRC not fully established. We investigated the clinicopathological features of T1 CRC and evaluated their association with lymph node metastasis in 133 cases of T1 CRC, consisting of 87 cases with first-line endoscopic resection (EMR) followed by additional surgery and 46 cases with primary surgical resection. Among the total 133 cases, 16 cases (12.0%) showed LN metastasis; 13 cases (13/16, 81.25%) were included in endoscopic resection cohort. These were all of the non-pedunculated gross type and most of LN+ tumors invaded submucosa over 1000 µm (surgical cohort versus endoscopic resection cohort; 3 versus 11). However, there was no statistical difference in the depth of submucosal invasion between the LN+ and LN- in both surgical cohort (2799.42 µm ± 401.56 versus 3000.00 µm ± 721.69, P = .897) and endoscopic resection cohort (2066.55 µm ± 142.96 versus 2305.77 µm ± 345.62, P = .520). Conversely, presence of and a higher number of tumor budding foci were associated with an increase in the incidence of LN metastasis in both cohort (P < .0001). Positive resection margins as well as absence of adenoma component were also an independent predictive factor for lymph node metastasis in 87 cases with first-line endoscopic resection followed by additional surgery. We found that tumor budding was the most reliable LN metastasis predictor in T1 CRC in both surgically resected and endoscopic resection specimens.

Occurrence of metachronous or synchronous lesions after endoscopic treatment of gastric epithelia dysplasia- impact of histologic features of background mucosa.

AIMS: Endoscopic resection is a safe and effective method to treat gastric epithelia dysplasia (GED). However, the development of metachronous and synchronous lesions after treatment has become a major concern. In this study, we investigated clinicopathologic features of 105 GED lesions from endoscopic resections between January 2008 and December 2009. Our goal is to find histologic factors that predict synchronous and metachronous lesions after ESD treatment. We assessed the degree of intestinal metaplasia (IM) and atrophy, type of IM, presence of gastritis cystica profunda, and crypt dysplasia in the adjacent mucosa. METHODS AND RESULTS: We divided 105 GED lesions into three groups: a single group without metachronous or synchronous GED or adenocarcinoma (n=35); a multiple synchronous group (n=30, group with synchronous occurrence of GED or adenocarcinoma after treatment); and a multiple metachronous group (n=40, group with metachronous occurrence of GED or adenocarcinoma after treatment). The multiple metachronous and synchronous groups showed larger sizes (p=0.003) and higher grades (p=0.021) as compared with the single group. Furthermore, marked IM and atrophy in adjacent mucosa were more easily seen in the multiple metachronous and synchronous groups as compared with the single group (p<0.0001). Interestingly, the presence of incomplete type of IM (p=0.025) and crypt dysplasia (p<0.0001) in background mucosa was associated with occurrence of metachronous and synchronous lesions following endoscopic resection of GED. CONCLUSIONS: The histological features of background mucosa, such as intestinal metaplasia, atrophy, and crypt dysplasia could be used as indicators of occurrence of metachronous and synchronous lesions after endoscopic treatment of GED.

Three cases of adrenocortical tumors mistaken for hepatocellular carcinomas/diagnostic pitfalls and differential diagnosis.

Adrenocortical adenomas and carcinomas in other parenchyma are extremely rare, with few cases reported and because of the rarity of these tumors, they occasionally cause problems during diagnosis. Adrenal cortical neoplasms in liver parenchyma can be present in 3 forms, including direct invasion or adhesion to liver parenchyma, tumors arising in adrenohepatic fusion tissue or in ectopic adrenal gland tissue. We report 3 cases of adrenal cortical tumors that were misdiagnosed as hepatocellular carcinoma in the preoperative state. The first case involved an adrenocortical adenoma arising in adrenohepatic fusion tissue. The remaining 2 cases involved an adrenocortical carcinoma and an adrenocortical oncocytoma arising in ectopic adrenal tissue in the liver. We describe the clinical presentations, gross, microscopic findings, immunohistochemical findings with respect to each case, with emphasis on differential diagnosis from hepatocellular carcinoma.

Programmed death-ligand 1 (PD-L1) expression in tumour cell and tumour infiltrating lymphocytes of HER2-positive breast cancer and its prognostic value.

Immunotherapy targeting PD-1/PD-L1 axis showed benefits in cancer. Prognostic significance of tumour infiltrating lymphocytes (TILs) has been determined. We evaluated PD-L1 protein expression in tumour cells and TILs, PD-L1 mRNA level and various histopathologic factors including TILs using 167 formalin-fixed paraffin embedded tissues and 39 fresh tissue of HER2-positive breast cancer. TILs level and PD-L1 expression in tumour cells and TILs were significantly correlated one another. PD-L1 positivity in tumour cells was associated with high histologic grade and high TILs level (p < 0.001, both). High PD-L1 immunoscore in TILs and high total immunoscore (in tumour cells and TILs) of PD-L1 were correlated with high histologic grade (p = 0.001 and p < 0.001, respectively), absence of lymphovascular invasion (p = 0.012 and p = 0.007, respectively), negative hormone receptor expression (p = 0.044 and p = 0.001, respectively) and high TILs level (p < 0.001, both). High PD-L1 mRNA expression was associated with high TILs level (p < 0.001, both). PD-L1 positivity in tumour cells was associated with better disease-free survival in HR-/HER2+ breast cancer (p = 0.039). PD-L1 expression in tumour cells and TILs are significantly associated with TILs level in HER2-positive breast cancer. PD-L1 expression in tumour cells might be positive prognostic factor in HR-/HER2+ breast cancers.

IDH1 R132C mutation is detected in clear cell hepatocellular carcinoma by pyrosequencing.

BACKGROUND: Isocitrate dehydrogenase 1 (IDH1) mutation is common in low-grade glioma (approximately 80%) and acute myeloid leukemia (approximately 10%). Other than brain tumor or hematologic malignancies, intrahepatic cholangiocarcinoma (iCC) is a well-known solid tumor with IDH1 mutation (6.8-20%). Histologically, poor differentiation and clear cell change are associated with IDH1 mutation in iCC. Since hepatocellular carcinoma (HCC) shares histologic features with iCC, some specific subtypes of HCC might show a higher IDH1 mutation rate than reported before (0.5-1.5%). METHODS: Forty-six cases of iCC and 48 cases of HCC (including 20 cases of clear cell type and 13 cases of pseudoglandular pattern) were tested for IDH1 mutation by pyrosequencing. RESULTS: Three cases in iCC (6.5%) and five cases in HCC (10.4%) had IDH1 mutation, all of which were Arg132Cys. IDH1 mutant HCCs were all clear cell type. Although the IDH1 mutation rate between iCC and HCC demonstrated no significant difference, clear cell HCC revealed statistically increased mutation rate compared to that of HCC without clear cell change (P = 0.009). Presence of IDH1 mutation was related with poor survival in clear cell HCC patients (P = 0.004). CONCLUSIONS: Clear cell HCC showed higher frequency of IDH1 mutation rate than other variants of HCC. This result consolidates the assumption that morphological features of tumors reflect molecular alterations.

VEGFR2 but not VEGFR3 governs integrity and remodeling of thyroid angiofollicular unit in normal state and during goitrogenesis.

Thyroid gland vasculature has a distinguishable characteristic of endothelial fenestrae, a critical component for proper molecular transport. However, the signaling pathway that critically governs the maintenance of thyroid vascular integrity, including endothelial fenestrae, is poorly understood. Here, we found profound and distinct expression of follicular epithelial VEGF-A and vascular VEGFR2 that were precisely regulated by circulating thyrotropin, while there were no meaningful expression of angiopoietin-Tie2 system in the thyroid gland. Our genetic depletion experiments revealed that VEGFR2, but not VEGFR3, is indispensable for maintenance of thyroid vascular integrity. Notably, blockade of VEGF-A or VEGFR2 not only abrogated vascular remodeling but also inhibited follicular hypertrophy, which led to the reduction of thyroid weights during goitrogenesis. Importantly, VEGFR2 blockade alone was sufficient to cause a reduction of endothelial fenestrae with decreases in thyrotropin-responsive genes in goitrogen-fed thyroids. Collectively, these findings establish follicular VEGF-A-vascular VEGFR2 axis as a main regulator for thyrotropin-dependent thyroid angiofollicular remodeling and goitrogenesis.

Combination of immunohistochemistry, FISH and RT-PCR shows high incidence of Xp11 translocation RCC: comparison of three different diagnostic methods.

We evaluated the frequency of translocation renal cell carcinoma (RCC) by reverse transcription polymerase chain reaction (RT-PCR) and how well the TFE3 immunoreactivity is concordant with TFE3 gene translocation status proved by fluorescence in situ hybridization (FISH) assay and RT-PCR. TFE3 and Cathepsin K expression was analyzed by immunohistochemistry in 185 RCC cases, and 48 cases either of more than weak expression of TFE3 or of positivity for Cathepsin K were done for FISH analysis and RT-PCR. All the RT-PCR positive cases were confirmed by cloning and sequencing. Of the 14 cases with strong nuclear TFE3 expression, 12 showed a break-apart signal by FISH. ASPL- and PRCC-TFE3 translocations were detected in 13 and one case, respectively, by RT-PCR. Of 21 cases with weak TFE3 expression, five were translocation-positive by FISH. ASPL-, PRCC-, and PSF-TFE3 translocations were detected by RT-PCR (n=3, 3, and 1, respectively). All 13 TFE3-negative/cathepsin K-positive cases were negative by FISH and two each harbored ASPL- and PRCC-TFE3 translocations that were detected by RT-PCR. A high rate of TFE3 immunoreactivity (8.6%) was confirmed by RT-PCR (13.5%) and FISH (9.7%). Higher translocation rate of RT-PCR means RT-PCR detected translocation in TFE3 weak expression group and only cathepsin K positive group more specifically than FISH. Thus, RT-PCR would complement FISH analysis for detecting translocation RCC with fusion partners.

Endoscopic submucosal dissection for papillary adenocarcinoma of the stomach: is it really safe?

BACKGROUND: Papillary adenocarcinoma of the stomach has been treated according to the same endoscopic submucosal dissection (ESD) indication criteria as other differentiated-type adenocarcinomas. We aimed to compare lymph node metastasis (LNM) in patients with early gastric cancer (EGC) with papillary adenocarcinoma (EGC-P) with that in patients with EGC with nonpapillary adenocarcinoma (EGC-NP) and to consider the potential limitation of current ESD indication criteria in the treatment of EGC-P. METHODS: In total, 1583 patients who underwent gastrectomy for EGC from 2005 to 2014 were included. Clinicopathologic characteristics of 56 patients with EGC-P were compared with those of 1527 patients with EGC-NP. The safety of ESD was evaluated, by application of current ESD indication criteria to EGC-P. RESULTS: The frequency of submucosal invasion was significantly higher in EGC-P than in both EGC-NP with differentiated-type histologic appearance and EGC-NP with undifferentiated-type histologic appearance (71.4% vs 50.8% and 37.6%, respectively). In addition, the frequency of LNM in EGC-P was 17.9%, higher than that in both EGC-NP with differentiated-type histologic appearance and EGC-NP with undifferentiated-type histologic appearance (9.7% and 11.1%, respectively). When the current ESD indication criteria were applied to the 56 patients with EGC-P, 17 patients met the current indications. Of these patients, two (11.8%) had LNM and three (17.6%) had lymphovascular invasion (LVI). When LNM and LVI were combined, one of seven patients (16.7%) meeting the absolute ESD indications and three of ten patients (30.0%) meeting the expanded ESD indications would not be cured after ESD. CONCLUSIONS: The use of ESD should be more carefully applied in patients with EGC-P meeting the ESD indication criteria, especially the expanded indication criteria, after pretreatment workup compared with other differentiated-type adenocarcinomas, owing to the higher frequencies of submucosal invasion, LNM, and LVI in EGC-P.

Expression of Myxovirus Resistance A (MxA) Is Associated with Tumor-Infiltrating Lymphocytes in Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancers.

PURPOSE: The prognostic significance of tumor-infiltrating lymphocytes (TILs) has been determined in breast cancers. Interferons can affect T-cell activity through direct and indirect mechanisms. Myxovirus resistance A (MxA) is an excellent marker of interferon activity. Here,we evaluated TILs and MxA expression in human epidermal growth factor receptor 2 (HER2)-positive breast cancers. MATERIALS AND METHODS: Ninety cases of hormone receptor (HR)+/HER2+ tumors and 78 cases of HR-/HER2+ tumors were included. The TILs level was assessed using hematoxylin and eosin-stained full face sections, and MxA expressionwas evaluated by immunohistochemistrywith a tissue microarray. RESULTS: MxA protein expression was significantly higher in tumors with high histologic grade (p=0.023) and high levels of TILs (p=0.002). High levels of TILs were correlated with high histological grade (p=0.001), negative lymphovascular invasion (p=0.007), negative lymph node metastasis (p=0.007), absence of HR expression (p < 0.001), abundant tertiary lymphoid structures (TLSs) around ductal carcinoma in situ (p=0.018), and abundant TLSs around the invasive component (p < 0.001). High levels of TILs were also associated with improved disease-free survival, particularly in HR-/HER2+ breast cancers. However, MxA was not a prognostic factor. CONCLUSION: High expression of MxA in tumor cells was associated with high levels of TILs in HER2-positive breast cancers. Additionally, a high level of TILs was a prognostic factor for breast cancer, whereas the level of MxA expression had no prognostic value.

Cardiac mucosa at the gastroesophageal junction: An Eastern perspective.

AIM: To investigate the nature and origin of cardiac mucosa (CM). METHODS: Biopsy samples from sixty-one individuals were included in this study. The specimens were taken "at", "just below", or "just above" the gastroesophageal junction, including the histologic squamocolumnar junction. Clinical data were obtained by reviewing electronic medical records for each patient. Patients with a history of stomach adenoma or carcinoma and esophageal carcinoma were excluded, and cases that were endoscopically suspicious of Barrett's esophagus or a polyp were also ruled out. Histologic and endoscopic reviews were performed blinded to the patient's clinical data. Histologic evaluation was conducted by two pathologists, and endoscopic review was performed by a endoscopist with wide experience in the field. Histologically, the columnar epithelium of squamocolumnar junction, presence and severity of acute and chronic inflammation, atrophy, intestinal metaplasia, and presence of carditis were evaluated. Endoscopically, reflux esophagitis was evaluated by Los Angeles (LA) classification, hiatal hernias were classified by Hill grade, and gastroesophageal flap valves were assessed. RESULTS: Fifty-nine of the 61 (96.7%) patients were Korean; 65.6% (40/61) of the patients underwent endoscopy according to the schedule of the National Health Insurance Program as a screening inspection. Of these, only 20.0% (8/40) of cases had reflux symptoms. CM was present in 41/61 (67.2%) individuals, and its presence was associated with older age compared to oxyntocardiac mucosa/oxyntic mucosa (60.59 ± 2.02 years vs 51.55 ± 3.35 years; P = 0.018). The presence of CM was associated with endoscopic diagnosis of esophagitis according to the LA classification (P = 0.022). CM was associated with mononuclear cell infiltration and neutrophilic infiltration, which were statistically significant (P = 0.001, and P = 0.004, respectively). The inflammation of CM, "carditis", showed a statistically significant association with endoscopic diagnosis of reflux esophagitis according to the LA classification (P = 0.008). CONCLUSION: CM at the gastroesophageal junction is a common histologic finding in biopsy specimens, though not always present, and associated with gastroesophageal reflux disease and carditis severity.

Histopathological features of the gastroesophageal junction: an Eastern view.

The definition and features of the gastroesophageal junction (GEJ) and the histopathologic features of the cardiac mucosa remain controversial. Most reports originate from western countries, which have different prevalence of GEJ adenocarcinoma and gastroesophageal reflux disease (GERD) compared to eastern countries. Therefore, we investigated GEJ anatomic and histopathologic features by histological mapping in 30 esophagogastrectomy specimens of middle and lower esophageal squamous cell carcinoma. We measured the lengths of the cardiac mucosa, oxyntocardiac mucosa, and esophageal cardiac-type glands. We assessed the presence of intestinal metaplasia, pancreatic acinar cells, Brunner's-like glands, and submucosal esophageal gland beneath cardiac mucosa and the relationship of these features with age and the circumferential location of cardiac mucosa. The lengths of cardiac mucosa and esophageal cardiac-type glands significantly increased with age (<63 years, 2767.86±734.95 µm vs. ≥63 years, 5453.12±839.52 µm, P=0.025 and <63 years, 1151.78±452.81 µm vs. ≥63 years, 2273.44±321.58 µm, P=0.049, respectively) and the presence of circumferential cardiac mucosa (+, 5731.25±721.57 vs. -, 2625.00±356.00 µm, P=0.007; +, 2425.00±326.13 µm vs. -, 400.00±204.80 µm, P<0.0001 respectively). The presence of intestinal metaplasia and irregular GEJ increased with age and the circumferential location of cardiac mucosa. The presence of esophageal submucosal glands beneath the cardiac mucosa, pancreatic acinar cells, and Brunner-like glands were seen in 8/30 (26.7%), 15/30 (50%), and 14/30 (46.7%) cases, respectively. These data indirectly suggest that cardiac mucosa originated from the distal esophagus and that the presence of cardiac mucosa may indicate GERD, in accordance with data from Western countries.

Yes associated protein is a poor prognostic factor in well-differentiated lung adenocarcinoma.

The Hippo pathway is a highly conserved potent regulator of cell growth and apoptosis including large tumor suppressor (LATS) and Yes-associated protein (YAP). LATS has been regarded as a tumor suppressor gene and YAP as either of a tumor suppressor gene or an oncogene. We investigated their expression in lung adenocarcinoma. YAP and LATS protein expression was assessed in 167 surgically resected lung adenocarcinomas and compared with clinicopathologic factors. Disease free survival and overall survival were also evaluated. YAP expression was noted in cytoplasm (48 cases; 28.7%), nuclear (34; 20.4%) and both locations (4; 2.4%). The nuclear expression was typically observed in well differentiated adenocarcinoma. LATS was expressed in cytoplasm when its signal is weak. Perinuclear expression of LATS was observed when it is strongly expressed. While cytoplasmic and nuclear YAP expressions were inversely related. In well differentiated adenocarcinoma patients, YAP nuclear expression was related with more frequent relapse. Both of nuclear YAP and LATS expression were more frequently observed in well differentiated adenocarcinoma. Furthermore, YAP expression exhibited more frequent relapse in well differentiated adenocarcinoma group. We suggest that YAP may act as an oncogene and predict poorer prognosis in well differentiated lung adenocarcinoma.