Significance of MUC1 and ß-Catenin Localization in Mucinous Carcinoma of the Breast.

BACKGROUND/AIM: There are two main subtypes of mucinous carcinoma (MC) based on the quantification of the mucinous component: the pure variant (pMC) and the mixed variant (mMC). pMC has been subdivided into pure A with a hypocellular variant, and pure B with a hypercellular variant. PATIENTS AND METHODS: We retrospectively analyzed the clinicopathological features of 99 patients with MC who were treated at our institution from January 2002 to December 2014. We evaluated the expression profiles of markers, including mucin (MUC) family members, in the patients groups representing different MC subtypes by performing immunohistochemistry to identify factors involved in the differentiation and progression of MCs. RESULTS: Among the 99 patients, 76 (76.8%) had pure mucinous carcinomas (pMC) and the other 23 (23.2%) had mixed mucinous carcinomas (mMC). Of the pMCs, 54 were pure A and 22 were pure B. The prognosis was worse for pure B than pure A and worse for mMC than pMC. Although there was no significant difference in clinicopathological factors between the pure A and pure B groups, immunohistochemical staining revealed differences in the localization of mucin MUC1 and ß-catenin. A comparison of the pMC and mMC cases revealed more lymphovascular invasion in mMC and differences in the localization of ß-catenin between the two groups. CONCLUSION: The patients' prognoses were significantly poorer depending on the histologic subtype (in the order pure A, pure B, and mixed). MUC1 localization and ß-catenin were revealed as independent predictors contributing to the poorer prognosis.

Tertiary lymphoid structures in tongue cancer: Association with clinicopathological parameters, preoperative S-1 chemotherapy response, and prognosis.

BACKGROUND: Tertiary lymphoid structures (TLSs) are observed in cancer-invasive sites of various organs, and show evidence of tumor-specific B and/or T cells, suggesting an active humoral antitumor response. The aim of this study was to evaluate the relationship between TLSs and prognosis in patients with tongue squamous cell carcinoma (TSCC) after preoperative S-1 chemotherapy. METHODS: Among 196 TSCC cases, 111 patients who received preoperative S-1 chemotherapy were compared to 85 patients who did not receive chemotherapy. We investigated the incidence of TLSs in both preoperative biopsy and resected specimens. RESULTS: TLSs were present in 24 (12%) biopsy specimens and 31 (16%) resected specimens. TLSs were associated with clinicopathologically advanced cases and positivity for lymphatic invasion. None of the cases with pStage 0 (i.e., noninvasive cancer) showed TLSs. In preoperative S-1 chemotherapy cases, TLSs were significantly more common in those treated with S-1 for more than 21 days and in those with treatment effects 0, Ia, and Ib. TLSs may not be a favorable prognostic factor by themselves but maybe a prognostic factor when combined with preoperative S-1 treatment. CONCLUSION: The presence of TLSs was suggested to be a factor indicating a favorable prognosis when considering the indication for preoperative S-1 chemotherapy. The synergistic effect of S-1 by activating antitumor immunity may be associated with a better prognosis in TSCC patients with TLSs.

A case of solitary digital glomus tumor associated with neurofibromatosis type 1.

An association between glomus tumor and neurofibromatosis type 1 has been reported. It is characterized by multiple tumors and young age at onset. The early diagnosis of neurofibromatosis type 1 is important because it is associated with a high rate of malignancy. A 25-year-old man presented to our hospital with left index finger pain that had persisted for 6 years. Physical and imaging findings suggested a benign soft-tissue tumor. Surgery was performed, and the tumor was pathologically diagnosed as glomus tumor. In this case, the patient with a young-onset glomus tumor was suspected of having neurofibromatosis type 1. An additional medical examination led to the diagnosis of unrecognized neurofibromatosis type 1. We experienced a case in which the onset of a glomus tumor led to the diagnosis of neurofibromatosis type 1. Comorbid neurofibromatosis type 1 should be kept in mind when glomus tumors are diagnosed.

Relationship between histopathological therapeutic effect and prognosis in oral cancer patients after preoperative S-1 chemotherapy followed by surgery.

OBJECTIVES: Preoperative S-1 chemotherapy is administered to prevent tumor proliferation before surgery in oral squamous cell carcinoma (OSCC). The aim of this study was to investigate the relationship between the histological therapeutic effect and prognosis in patients with OSCC after pre-operative S-1 chemotherapy. MATERIALS AND METHODS: Among 461 OSCC cases, 281 patients who received preoperative S-1 chemotherapy were compared with 180 patients that did not receive chemotherapy to determine the histological therapeutic effect in the resected specimens and the differences in relapse-free survival. RESULTS: The histological chemotherapeutic effect was well correlated with the subsequent prognosis. In an examination of the combined effect of treatment and ypStage, the groups with good S-1 treatment effects had extremely good prognoses, even if the postoperative resection specimens were within the same ypStage. In a stratified search of patients who received S-1 for more than 7 days and who had a significantly better prognosis than those who did not receive S-1, it was found that the prognosis was significantly better for patients with tongue cancer according to site; furthermore, tongue cancer, age under 70 years of age, male sex, and clinical stage I were factors associated with a significantly better prognosis. CONCLUSIONS: Even if the postoperative resection specimens were within the same ypStage, the groups that responded to S-1 treatment were considered to have extremely good prognoses. CLINICAL RELEVANCE: A good adaptation for S-1 was tongue cancer, and especially tongue cancer with cStage I, male sex, and age less than 70 years old.

Sigmoid colon schwannoma difficult to distinguish from peritoneal dissemination 13 years after pancreatic neuroendocrine tumor surgery.

BACKGROUND: Schwannoma, which clinicians sometimes struggle to diagnose, is a tumor arising from Schwann cells of peripheral nerves, often in the soft tissues and rarely in the gastrointestinal tract. Pancreatic neuroendocrine tumor (PNET) is rare among pancreatic tumors, and recurrence can occur long after resection. Here, we were presented with a case where a sigmoid colon schwannoma was difficult to distinguish from a postoperative recurrence of PNET and was diagnosed after laparoscopic resection. CASE PRESENTATION: A 51-year-old man was diagnosed with PNET (NET G2) after a distal pancreatectomy (DP) 13 years ago. The patient underwent hepatectomy due to liver metastasis 12 years after initial radical surgery. The follow-up magnetic resonance imaging (MRI) after hepatectomy showed pelvic nodules, and laparoscopic surgery was performed for both diagnosis and treatment because peritoneal dissemination of PNET could not be ruled out. Since the tumor was in the sigmoid colon, a partial colon resection was performed. The histopathological diagnosis was a schwannoma, and the patient was discharged on the seventh postoperative day. CONCLUSIONS: We experienced a case of sigmoid colon schwannoma that was difficult to differentiate from peritoneal dissemination of PNET and was later diagnosed after laparoscopic resection. In addition, this case involved a long-term postoperative recurrence of PNET that was amenable to radical resection, further establishing the importance of long-term imaging follow-up.

Case of pneumatosis cystoides intestinalis with intra-abdominal free air developed during treatment with voglibose.

Contrast-enhanced computed tomography (CT) scan (portal phase) at the onset. Emphysema is detected in the ileal wall (b, c: Arrows) and free air is detected in the abdominal cavity (a: Arrowhead). CT scan imaging settings: (a-c) window level (WL) 60 and window width (WW) 300. (d-f) WL 0 and WW 433. By changing the imaging settings, intestinal emphysema and free air can be more easily identified.

Molecular and expressional characterization of tumor heterogeneity in pulmonary carcinosarcoma.

The genetic concordance and heterogeneity of the two components of pulmonary carcinosarcoma (PCS), carcinoma, and sarcoma, have not been fully elucidated because of its rare occurrence. We performed targeted sequencing of the carcinoma and sarcoma components of four PCSs to identify genetic similarities and differences. Formalin-fixed paraffin-embedded tissue samples were macroscopically or microscopically dissected. DNA was extracted from each component, and genetic alterations were analyzed separately. Moreover, we performed RNA-seq analysis on both components of one PCS to compare differences in gene expression profiles. The carcinoma part consisted of adenocarcinoma in two cases, squamous cell carcinoma in one, and adenosquamous carcinoma in the last. TP53 mutation was observed in three samples from the trunk, although it was detected only in the sarcoma part in one case. No specific driver gene mutation was observed; however, KRAS mutations were observed in one case in the trunk. RNA-seq analysis revealed that the rhabdomyosarcoma component expressed various genes related to muscle development, whereas the carcinoma component did not; and that gene expression overall was completely different between the two components. Our study revealed that the two different components of PCS shared common gene mutations in most cases. Although gene expression was different among components, if driver genes such as KRAS were detected in PCS, molecular targeted therapy could be beneficial even when the tumor contains a sarcoma component.

Ghost cell odontogenic carcinoma arising in dentinogenic ghost cell tumor with next-generation sequencing cancer panel analysis: A case report.

OBJECTIVE: Ghost cell odontogenic carcinoma (GCOC) is a rare tumor that can sometimes occur from dentinogenic ghost cell tumor (DGCT). STUDY DESIGN: We report a case of GCOC arising from DGCT that underwent long-term follow-up with multiple biopsies. The biopsy specimens were analyzed using a next-generation sequencing cancer panel. RESULTS: Histopathology of the resected tumor revealed that the boundary between benign and malignant components was clear. In immunohistochemistry, the nuclei of malignant tumor cells were positive for ß-catenin and LEF-1. CTNNBI mutation was detected in all 4 biopsy specimens, and all of these mutations were identical (c.98C>G (p.Ser33Cys)). No other gene mutations that could definitively cause malignant transformation were detected. CONCLUSIONS: This case suggested that GCOC and DGCT are ghost cell neoplasms caused by a common mutation of CTNNB1 and that the malignant cells of GCOC are derived from cells that specifically differentiate into ghost cells.

Multimodal immunotherapy ameliorates myasthenia gravis preceded by thymoma-associated multiorgan autoimmunity.

Thymoma-associated multiorgan autoimmunity (TAMA) is a rare autoimmune disorder associated with thymoma that causes a pathology similar to graft-versus-host disease (GVHD) targeting the skin, digestive organs, and liver. Herein, we report the case of a 38-year-old male with myasthenia gravis (MG) preceded by TAMA. The patient developed intractable diarrhea 2 years before admission. Subsequently, dysphagia, dysarthria, and left blepharoptosis were observed. The patient was admitted to the hospital because of fever and dyspnea, was positive for anti-AChR antibody, and chest-computed tomography revealed thymoma, which led to the diagnosis of thymoma-related MG. Biopsied specimens from the sigmoid colon revealed apoptotic colonopathy with lymphocyte-rich lamina propria. Immunohistochemical staining revealed that the infiltrating cells were predominantly labeled with anti-CD3-antibody. The patient did not show skin lesions or liver dysfunction. Therefore, TAMA limited to the gastrointestinal tract was diagnosed. Although TAMA typically has a poor prognosis, immediate multimodal immunotherapy for MG was successful, resulting in a good outcome for TAMA of this case. TAMA is caused by the inability of the thymoma to suppress self-reactive T lymphocytes, which subsequently leads to a disease that is clinically indistinguishable from GVHD. Based on the characteristics of this case, limited gastrointestinal tract involvement in TAMA without lesions in other organs may lead to a favorable prognosis. TAMA cases lacking skin lesions may present with nonspecific gastrointestinal or liver disease. If a patient with thymoma-associated MG has gastrointestinal symptoms such as diarrhea, TAMA should be considered, and the diagnosis should be made early by pathological evaluation of gastrointestinal tissues.

Salvage thoracoscopic esophagectomy after carbon-ion radiotherapy in a patient with esophageal squamous cell carcinoma: a case report.

BACKGROUND: Carbon-ion radiotherapy (CIRT) for esophageal cancer has been receiving significant attention given its high local control rates and minimal damage to normal tissues. However, the efficacy and safety of salvage surgery after CIRT for esophageal cancer remain unclear. We report the case of a patient who underwent salvage thoracoscopic surgery after CIRT. CASE PRESENTATION: A 51-year-old woman underwent upper gastrointestinal endoscopy and a type 0-IIa + 0-IIc esophageal squamous cell carcinoma located 27-29 cm from the patient's incisors, classified as clinical stage I (T1bN0M0), was detected. She received CIRT (50.4 Gy [relative biological effectiveness, RBE]/12 fr) for localized esophageal cancer and achieved complete remission after 4 months. Six years after CIRT, follow-up endoscopic examination demonstrated a type 0-IIa + 0-IIc tumor in the previously treated area. In addition, a type 0-IIa lesion located 20-22 cm from the incisors was found. We diagnosed localized ESCC, classified as clinical stage I (T1bN0M0). Salvage thoracoscopic surgery was performed in the prone position with five access ports. Although the esophagus tightly adhered to the thoracic descending aorta and left main bronchus with severe fibrosis, the esophagus could be separated from the surrounding organs with careful forceps manipulation. The operation time and blood loss were 8 h 45 min and 253 mL, respectively. The patient was discharged from our hospital 17 days after the salvage surgery without any complications. Pathological findings revealed two squamous cell carcinomas. Both tumors were localized in the lamina propria mucosa, and lymph node metastasis was not detected. The tumors were diagnosed as pathological stage IA (pT1aN0M0) according to the TNM criteria. Moreover, pathological examinations showed severe fibrosis of the previously irradiated tissues compared to the normal esophagus located outside of the irradiation field. Following the surgery, the patient had no recurrence for 1 year and 6 months. CONCLUSIONS: Thoracoscopic radical esophagectomy can be performed as salvage surgery. Careful and discreet surgery is integral to perform salvage surgery after CIRT since CIRT may cause severe adhesions and fibrosis in the irradiated field.

Nuclear morphology in breast lesions: refining its assessment to improve diagnostic concordance.

AIMS: Although evaluation of nuclear morphology is important for the diagnosis and categorisation of breast lesions, the criteria used to assess nuclear atypia rely upon the subjective evaluation of several features that may result in inter- and intraobserver variation. This study aims to refine the definitions of cytonuclear features in various breast lesions. METHODS AND RESULTS: ImageJ was used to assess the nuclear morphological features including nuclear diameter, axis length, perimeter, area, circularity and roundness in 160 breast lesions comprising ductal carcinoma in situ (DCIS), invasive breast carcinoma of no special type (IBC-NST), tubular carcinoma, usual ductal hyperplasia (UDH), columnar cell change (CCC) and flat epithelial atypia (FEA). Reference cells included normal epithelial cells, red blood cells (RBCs) and lymphocytes. Reference cells showed size differences not only between normal epithelial cells and RBCs but also between RBCs in varied-sized blood vessels. Nottingham grade nuclear pleomorphism scores 1 and 3 cut-offs in IBC-NST, compared to normal epithelial cells, were < ×1.2 and > ×1.4 that of mean maximum Feret's diameter and < ×1.6 and > ×2.4 that of mean nuclear area, respectively. Nuclear morphometrics were significantly different in low-grade IBC-NST versus tubular carcinoma, low-grade DCIS versus UDH and CCC versus FEA. No differences in the nuclear features between grade-matched DCIS and IBC-NST were identified. CONCLUSION: This study provides a guide for the assessment of nuclear atypia in breast lesions, refines the comparison with reference cells and highlights the potential diagnostic value of image analysis tools in the era of digital pathology.

Mesenteric phlebosclerosis associated with the oral intake of Japanese traditional (Kampo) medicines containing Gardeniae Fructus.

We report a case of mesenteric phlebosclerosis (MP) in a woman in her 50s who had been taking Kamishoyosan for 13 years. Colonoscopic findings 13 years after the start of oral administration were nonspecific, with decreased vascular permeability and redness of the mucosa. The extent of the lesion was initially from the cecum to the ascending colon but expanded over time to the transverse colon. In colon biopsies, there was a remarkable deposition of collagen fibers around the small vessels in the lamina propria of the cecum or the ascending colon over time, and the specific lesions expanded to the transverse colon. The deposition of collagen fibers around the vessels in the lamina propria was already present when the total oral dose of the Sanshishi component was low. In this valuable case of MP, changes after the start of oral administration of Kamishoyosan could be followed over time via endoscopy and biopsy.

CD15+ tumor infiltrating granulocytic cells can predict recurrence and their depletion is accompanied by good responses to S-1 with oral cancer.

BACKGROUND: It has been reported in oral squamous cell carcinoma (OSCC) that myeloid-derived suppressor cells infiltrate tumor tissues. This study examined whether S-1 chemotherapy changes immune cell populations in the tumor microenvironment. METHODS: We examined 71 patients with of OSCC, including 51 patients who received preoperative S-1 chemotherapy. Immunohistochemistry for PD-L1, CD8, forkhead box protein 3 (FOXP3), and CD15 was performed using biopsy and resected specimens. RESULTS: The numbers of CD8+ , FOXP3+ , and CD15+ cells in resected specimens were significantly decreased by S-1 chemotherapy. The reduction of the proportion of CD15+ cells significantly differed between responders and nonresponders. Most responders were distributed into the group with low PD-L1 expression and a low density of CD8+ cells before chemotherapy. Furthermore, many patients with recurrence exhibited a high density of CD15+ cells in biopsy specimens. CONCLUSION: Preoperative S-1 chemotherapy can potentially improve prognosis by reducing CD15+ cells in the tumor microenvironment.

A mucinous cystic neoplasm of the pancreas containing an undifferentiated carcinoma component and harboring the NRAS driver mutation.

A woman in her 20s visited our hospital with a chief complaint of abdominal distension and back pain. She was diagnosed with a cystic tumor (diameter 16 cm) in the tail of the pancreas and underwent a combined distal pancreatectomy, splenectomy, and left adrenalectomy. Histopathologically, the tumor presented as a mucinous cystic neoplasm with an undifferentiated carcinoma component of the pancreas. In addition, the cells demonstrated a partial rhabdoid-like morphology. These findings were considered relatively typical for a mucinous cystic neoplasm in the tail of the pancreas in a young woman. However, NRAS mutation, which is rare in pancreatic tumors, was detected.

Adenocarcinoma with intraductal papillary mucinous neoplasm arising in a duodenal heterotopic pancreas: a case report.

A woman in her 70 s was diagnosed with a tumor in her duodenal wall during a routine visit for diabetes. She subsequently underwent subtotal stomach-preserving pancreatoduodenectomy. Histologically, the tumor was present mainly in the duodenal wall, and atypical cystic ducts were seen in the muscularis propria and subserosa. Invasive well-differentiated adenocarcinoma was seen in the duodenal submucosal and mucosal layers. Heterotopic pancreatic tissue was seen within the tumor, and atypical epithelium had proliferated and replaced the cystic ductal epithelium of the heterotopic pancreas. Therefore, adenocarcinoma with intraductal papillary mucinous neoplasm arising in duodenal heterotopic pancreas was the final histopathological diagnosis, which is considered rare.

Liver metastasis from papillary thyroid carcinoma treated by laparoscopic hepatectomy 43 years after resection of the primary tumor: a case report.

BACKGROUND: Papillary thyroid carcinoma (PTC) generally has a good prognosis, while liver metastasis from PTC is rare and difficult to diagnose. CASE PRESENTATION: A 67-year-old woman was diagnosed with PTC and underwent a left hemithyroidectomy 43 years ago. Two years ago, thoracoscopic right middle lobectomy was performed for a lung tumor, and pathology reports confirmed a metastatic lung tumor of PTC. The patient was followed up regularly with computed tomography, and a liver tumor measuring 16 mm was found in the lateral segment of the liver. Fluorodeoxyglucose positron emission tomography (FDG-PET) was negative for liver tumor. However, FDG uptake was observed at the nodule outside the right lobe of the thyroid gland, suggesting metastasis to the right supraclavicular lymph node. Laparoscopic partial S2 hepatectomy was performed without complications. The final diagnosis was metastatic liver tumor from PTC, and the surgical margins were free of tumor. Postoperatively, the patient underwent complementary thyroidectomy and right supraclavicular lymph node dissection, followed by I-131 ablation. The final diagnosis was PTC of 7 mm and 4 mm and lymph node metastasis of 9 mm. The patient is currently doing well and has had no recurrence 1 year after surgery. CONCLUSIONS: This case demonstrates that liver metastases from PTC may be found after long-term follow-up, and liver resection might be the most appropriate treatment.

Diagnostic value of 18F-FDG-PET to predict the tumour immune status defined by tumoural PD-L1 and CD8+tumour-infiltrating lymphocytes in oral squamous cell carcinoma.

BACKGROUND: Lately, immune checkpoint proteins, such as programmed death 1 (PD-1) and its ligand-1 (PD-L1), have garnered attention as a new target in oral squamous cell carcinoma (OSCC). Reportedly, fluoro-D-glucose (FDG)-uptake alteration by anti-PD-1 antibody treatment depicts the response in patients with lung cancer. This study aims to elucidate the correlations between tumour immune status, clinicopathological factors, 18F-FDG-uptake and cold tumour phenotypes as low PD-L1 expression/low CD8+tumour-infiltrating lymphocytes (TILs) in OSCC. METHODS: We performed immunohistochemical analysis of PD-L1, hypoxia-inducible factor 1 A (HIF-1A), glucose transporter type 1 (GLUT1), CD8, E-cadherin and Ki-67 on 59 operable OSCC samples. We assessed the correlations between these factors and preoperative 18F-FDG-uptake, clinicopathological characteristics and prognosis. RESULTS: Low expression of PD-L1 in OSCC correlated with cancer aggressiveness, poor prognosis, high 18F-FDG-uptake with HIF-1A/GLUT1 and low E-cadherin expression and low CD8. Cold tumour phenotypes as low PD-L1 tumour cells and low stromal CD8 correlated with the poor prognosis, high 18F-FDG-uptake and E-cadherin suppression. Furthermore, the high level of preoperative 18F-FDG-uptake in OSCC was an independent predictor of the cold tumour immune status. CONCLUSIONS: 18F-FDG-uptake is an independent predictor of cold tumour in OSCC. 18F-FDG-PET imaging could be a promising diagnostic tool to estimate tumour immune status.

An immunohistochemical and genetic study of BRAFV600E mutation in Japanese patients with ameloblastoma.

Ameloblastoma is an odontogenic tumor of the jaw. It most frequently occurs in the mandible, and less often in the maxilla. Mandibular ameloblastoma harbors a BRAF mutation that causes a valine (V) to glutamic acid (E) substitution at codon 600 (BRAFV600E ). We examined specimens from 32 Japanese patients to detect the prevalence of the BRAFV600E mutation, and to evaluate the relationship between immunohistochemical (IHC) expression and genetic results, of BRAFV600E+ ameloblastoma. Among the 32 cases, 22 (69%) were IHC positive for BRAFV600E protein, and 10 (31%) were IHC negative; and polymerase chain reaction showed 16 of 21 tested cases (76%) carried the BRAFV600E mutation. Our findings indicate that that samples that stain IHC positive for BRAFV600E protein are more likely to carry the BRAFV600E mutation. These results support assessments for BRAF mutations, and the use of BRAF inhibitors as targeted therapy for ameloblastoma in Japanese patients.

Histopathological changes in tumor budding between biopsy and resected specimens from patients treated with preoperative S-1 chemotherapy for oral cancer.

BACKGROUND: S-1 is an oral anticancer agent containing tegafur, a prodrug of 5-fluorouracil (5-FU). Preoperative S-1 chemotherapy is performed to prevent tumor proliferation before surgery in oral squamous cell carcinoma (OSCC). The aim of this study was to evaluate the effects of preoperative S-1 chemotherapy on tumor budding. METHODS: We examined 248 cases of OSCC and evaluated the budding scores in biopsy and resected specimens by keratin immunohistochemistry. RESULTS: In S-1-untreated patients, the budding scores in resected specimens tended to show a mild increase. S-1 treatment had the effect of lowering the budding score, although some cases with dramatically increased budding scores in resected specimens were found in the early phase of administration. Relapse-free survival showed a significant difference (P < .01) according to the presence or absence of S-1 treatment among patients with high budding scores. CONCLUSIONS: The present findings indicate that S-1 administration may be more effective in patients with high budding scores than in those with lower budding scores.

High expression of forkhead box protein C2 is associated with aggressive phenotypes and poor prognosis in clinical hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the major causes of tumor death; thus, the identification of markers related to its diagnosis and prognosis is critical. Previous studies have revealed that epithelial-to-mesenchymal transition (EMT) is involved in tumor invasion and metastasis, and the forkhead box protein C2 (FOXC2) has been shown to promote tumor cell proliferation, invasion, and EMT. In the present study, we examined the clinicopathological significance of FOXC2 and EMT-related markers in clinical HCC specimens and identified factors related to the diagnosis and prognosis of HCC. METHODS: The expression of FOXC2 and EMT-related markers was evaluated by immunohistochemistry in 84 cases of hepatocellular carcinoma. RESULTS: A high expression of FOXC2 was observed in 26 of 84 cases, and expression was significantly correlated with background liver cirrhosis, poor tumor differentiation, high serum AFP, and elevated cell proliferation markers. In addition, this high expression was related to the induction of the Cadherin switch and vimentin expression and was an independent predictor for poor prognosis. CONCLUSION: The high expression of FOXC2 in HCC is correlated with tumor malignancy and poor prognosis, suggesting that FOXC2 may be an important prognostic factor for HCC.