Carcinomatous meningitis from recurrent glassy cell carcinoma of the uterine cervix-A case report.

Carcinomatous meningitis presents with a variety of neurological symptoms and has a poor prognosis. We encountered a case of carcinomatous meningitis from cervical cancer. A 30-year-old patient was diagnosed with cervical cancer (glassy cell carcinoma), stage IIB. She underwent radical hysterectomy and chemoradiotherapy. Nine months later, the disease recurred with iliac lymph node and right lung metastases. The patient received chemotherapy; however, after seven cycles, the lung lesions increased. The patient responded to supportive care; nevertheless, symptoms including headaches developed and were followed by diplopia. A contrast-enhanced magnetic resonance image of the head confirmed the diagnosis of carcinomatous meningitis. She was transferred to the palliative care unit and died approximately 1 week later. Carcinomatous meningitis has a poor prognosis and is difficult to treat; however, early diagnosis may provide meaningful time to patients. Therefore, attention must be paid to meningeal irritation and neurological symptoms.

[Primary Pericardial Dedifferentiated Liposarcoma Detected by Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography;Report of a Case].

We herein present a rare case of dedifferentiated liposarcoma originating from the pericardium. A 79-year-old female was referred to our hospital with a pericardial tumor detected by fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT). The tumor, 80×48 mm in size, showed increased uptake of fluorodeoxyglucose on the FDG-PET/CT without any evidence of metastasis. The tumor was resected with the pericardium, and a histopathological examination confirmed the diagnosis of dedifferentiated liposarcoma. Additional chemotherapy, radiation therapy, or a combination of both were offered but refused by the patient. Although the patient was discharged without any complications, the tumor recurred locally 2 months after the surgery, and the patient succumbed 15 months later. The FDG-PET/CT was useful not only in detecting this malignant tumor but also in diagnosing its malignant nature.

Clinical Utility of Endometrial Cell Block Cytology in Postmenopausal Women.

OBJECTIVE: To investigate the diagnostic utility of endometrial (EM) cell block (CB) cytology for the detection of intrauterine malignancy in postmenopausal women. METHODS: We reviewed the medical records of 104 postmenopausal women between January 2012 and November 2014. We reviewed symptoms upon admission, body mass index, parity, transvaginal ultrasonographic findings, and histopathological results based on CB and conventional cytology. RESULTS: The mean age was 62.6 (range 48-95) years. The mean menopausal age was 50.8 years and the mean duration of menopause was 12.0 years. The sensitivity of CB and conventional cytology was 82.3% (29/35) and 85.7% (30/35) and the specificity was 98.6% (68/69) and 94.2% (65/69), respectively. The sensitivity and specificity of CB cytology combined with conventional cytology were 82.3% (29/35) and 94.2% (65/69), respectively. The predictive values for EM hyperplasia and type-II carcinoma were 100 and 85.7%, respectively. CONCLUSION: CB cytology provides specimens for examination in a single outpatient session. Additionally, immunohistochemical staining can provide useful information for histological diagnosis. A combination of CB and conventional cytology can improve the diagnostic accuracy of EM lesions and may be a valid method for screening in postmenopausal women.

Detection of serous precursor lesions in resected fallopian tubes from patients with benign diseases and a relatively low risk for ovarian cancer.

The frequency of ovarian cancers in Japan has increased; however, doubts have been raised concerning the mechanism by which high-grade serous adenocarcinomas (HGSCs) arise. Conventionally, HGSC is thought to originate from the ovarian surface epithelium or epithelial inclusion cyst. However, recent data indicate that HGSCs may in fact develop from precursor lesions in the fallopian tube, including epithelia with a p53 signature, serous tubal intraepithelial carcinomas (STICs), secretory cell outgrowths (SCOUTs), and tubal intraepithelial lesions in transition (TILT). Here, we determined the frequency of these fallopian tube precursors in surgically excised samples from 123 patients with benign pelvic diseases. We identified 12 cases with a p53 signature (9.7%), 26 with observable SCOUTs (21.1%), and 4 with TILT (3.2%), but no STIC cases. Although the lifetime risk for developing ovarian cancer is only around 1.4% for women without germ-line mutations, it is important to evaluate the presence of precursor lesions to understand HGSC pathogenesis better. Taken together, salpingectomy appears to be an option for women who are past their childbearing age and plan to undergo elective pelvic surgery. To our knowledge, this is the first study to investigate the presence of these specific precursors post-salpingectomy in low-risk patients.

Adult pancreatic hemangioma: A case report.

Vascular neoplasms of the pancreas are extremely rare and usually manifest as symptomatic, cystic lesions. This study presents a case that includes the clinicopathologic information used to discriminate pancreatic hemangioma from other types of cystic lesion of the pancreas. A 40-year-old female visited hospital with a chief complaint of abdominal pain. The serum CEA and CA19-9 levels of the patient were within the normal limits. An abdominal computed tomography scan and magnetic resonance imaging showed a 100-mm mass lesion in the body and tail of the pancreas, and the tumor extended toward the retroperitoneum and surrounded the splenic vein. The lesion was subsequently resected. Macroscopically, it was a multiloculated cyst with intracystic hemorrhage. Microscopically, the lesion was composed of numerous, heterogeneous cysts lined by a flattened single layer of cells without significant atypia. Notably, numerous neoplastic vessels extended into the interlobular septa of the pancreas and surrounded the main pancreatic duct. Immunohistochemical analysis showed that the lining cells expressed CD31 and CD34. The lesion was diagnosed as adult pancreatic hemangioma. Surgical treatment may be required when a direct contact between the lesion and the pancreatic tissue is demonstrated using imaging.

Squamous cell carcinoma with apocrine features of the breast: A case report.

A rare case of squamous cell carcinoma (SCC) with apocrine features was investigated; the focus was on the histological characteristics of the cancer cells in a 68-year-old female exhibiting an ulcerated lesion of the right breast. Diagnostic imaging methods identified a lobulated solid tumor and indicated multiple enlarged lymph nodes in the left axilla, which confirmed the diagnosis of advanced breast cancer; thus, a mastectomy was performed. Macroscopic investigations identified the tumor as a white, solid lesion measuring 66 × 68 × 47 mm, which exhibited necrosis. Histologically, the tumor was predominantly solid and exhibited nest patterns, in addition to intracellular keratinization. Immunohistochemical staining identified the tumor cells as positive for cytokeratin 5/6, 34ßE12 and P63. The lesion was considered to be an SCC demonstrating negative expression for the human epidermal growth factor receptor 2, estrogen receptor and progesterone receptor; therefore, the tumor was a triple-negative breast cancer. Conversely, approximately one-third of the tumor cells indicated abundant eosinophilic cytoplasm and gross cystic disease fluid, which was demonstrated via protein-15 staining; this indicated the presence of apocrine features. In addition, the androgen receptor was expressed in the tumor cells, thus the lesion was diagnosed as an SCC of the breast, exhibiting apocrine features.

Intraductal neoplasm of the intrahepatic bile duct: clinicopathological study of 24 cases.

AIM: To investigate the clinicopathological features of intraductal neoplasm of the intrahepatic bile duct (INihB). METHODS: Clinicopathological features of 24 cases of INihB, which were previously diagnosed as biliary papillomatosis or intraductal growth of intrahepatic biliary neoplasm, were reviewed. Mucin immunohistochemistry was performed for mucin (MUC)1, MUC2, MUC5AC and MUC6. Ki-67, P53 and ß-catenin immunoreactivity were also examined. We categorized each tumor as adenoma (low grade), borderline (intermediate grade), and malignant (carcinoma in situ, high grade including tumors with microinvasion). RESULTS: Among 24 cases of INihB, we identified 24 tumors. Twenty of 24 tumors (83%) were composed of a papillary structure; the same feature observed in intraductal papillary neoplasm of the bile duct (IPNB). In contrast, the remaining four tumors (17%) showed both tubular and papillary structures. In three of the four tumors (75%), macroscopic mucin secretion was limited but microscopic intracellular mucin was evident. Histologically, 16 tumors (67%) were malignant, three (12%) were borderline, and five (21%) were adenoma. Microinvasion was found in four cases (17%). Immunohistochemical analysis revealed that MUC1 was not expressed in the borderline/adenoma group but was expressed only in malignant lesions (P = 0.0095). Ki-67 labeling index (LI) was significantly higher in the malignant group than in the borderline/adenoma group (22.2 ± 15.5 vs 7.5 ± 6.3, P < 0.01). In the 16 malignant cases, expression of MUC5AC showed borderline significant association with high Ki-67 LI (P = 0.0622). Nuclear expression of ß-catenin was observed in two (8%) of the 24 tumors, and these two tumors also showed MUC1 expression. P53 was negative in all tumors. CONCLUSION: Some cases of INihB have a tubular structure, and are subcategorized as IPNB with tubular structure. MUC1 expression in INihB correlates positively with degree of malignancy.

N-myc downstream regulated gene 1 (NDRG1)/Cap43 enhances portal vein invasion and intrahepatic metastasis in human hepatocellular carcinoma.

N-myc downstream regulated gene 1 (NDRG1)/Cap43 is a 43 kDa protein that is widely distributed in the body. Its expression is regulated by nickel, cobalt, hypoxic condition and others; it is reported to be weaker in tumors than normal tissues; and NDRG1/Cap43 is considered to act suppressively to tumor metastasis. This current study immunohistochemically examined NDRG1/Cap43 expression in hepatocellular carcinoma (HCC), and analyzed its relationship to clinicopathologic factors and prognosis. The samples were 105 surgically resected HCC tissue blocks, i.e., 18 well-differentiated HCC, 61 moderately differentiated HCC, 10 poorly differentiated HCC, 9 'nodule-in-nodule' type HCC, and 7 sarcomatous HCC. In all cases, NDRG1/Cap43 was not expressed in normal liver cells. Strong expression was found in 65 of the 105 cases (62%), i.e., in 11.1% of well-differentiated HCC, 72.1% of moderately differentiated HCC, 80.0% of poorly differentiated HCC, and 71.4% of sarcomatous HCC. In the 'nodule-in-nodule' type, its expression was found in 55.6% of their well-differentiated component, and this frequency was significantly higher than that in well-differentiated HCC (11.1%). In the cases showing strong NDRG1/Cap43 expression, frequency of portal vein invasion and of intrahepatic metastasis was significantly high. No clear relationship between the expression and prognosis was observed. NDRG1/Cap43 expression that was found in advanced HCC was thought to accelerate tumor invasion and metastasis. NDRG1/Cap43 could act as a useful biomarker of HCC.

Growth inhibitory effects of pegylated IFN-alpha2b and 5-fluorouracil in combination on renal cell carcinoma cell lines in vitro and in vivo.

We investigated the effects of pegylated IFN-alpha2b (PEG-IFN-alpha2b) alone and PEG-IFN-alpha2b plus 5-fluorouracil (5-FU) in vitro on the proliferation of renal cell carcinoma (RCC) cell lines. After the transplantation of RCC cells into nude mice, we administered IFN (PEG-IFN-alpha2b or IFN-alpha2b) alone, 5-FU alone, or IFN (PEG-IFN-alpha2b or IFN-alpha2b) plus 5-FU; and investigated tumor volume, tumor weight, the numbers of apoptotic cells and artery-like blood vessels, relative mRNA expression levels of enzymes which relate to 5-FU metabolism, angiogenesis factor, and type I interferon receptor. RCC cells in vitro were generally and relatively resistant to the anti-proliferative effects of PEG-IFN-alpha2b, but the addition of 5-FU augmented IFN-induced anti-proliferative effects with the induction of apoptosis. PEG-IFN-alpha2b in vivo presented stronger anti-tumor effects than IFN-alpha2b, and its combination with 5-FU augmented the effects. The significant anti-tumor effect of the combination treatment was the increase in apoptotic cell number, but there were no significant differences in the suppression of angiogenesis, expression of IFN receptor, and the actions of metabolic enzymes of 5-FU. In conclusion, PEG-IFN-alpha2b presents stronger anti-tumor effects than non-pegylated IFN, and the effects are augmented in the combination with 5-FU. Our findings suggest the clinical usefulness of PEG-IFN-alpha2b in the treatment of RCC.

Cap43/NDRG1/Drg-1 is a molecular target for angiogenesis and a prognostic indicator in cervical adenocarcinoma.

Cap43 is a nickel- and calcium-inducible gene that plays important roles in the primary growth of malignant tumors, as well as in invasion and metastasis, most likely through its ability to induce cellular differentiation. This study investigated associations of Cap43 expression with angiogenesis and other clinicopathological factors in cervical adenocarcinoma. The clinical records of 100 women who underwent surgery for cervical adenocarcinoma were reviewed retrospectively. Microvessel density and the expression of Cap43 and VEGF in the surgical specimens were evaluated immunohistochemically. The Cap43 expression level was significantly associated with angiogenesis, tumor diameter, stromal invasion, lymphovascular space invasion, lymph node metastasis, and histopathological differentiation. Kaplan-Meier analysis showed a significant association between the Cap43 expression level and survival: high Cap43 expression was related to poor survival. Our results suggest that increased expression of Cap43 is associated with angiogenesis and may be a poor prognostic indicator in women with cervical adenocarcinoma.

Overexpression of the myc target gene Mina53 in advanced renal cell carcinoma.

The myc target gene Mina53 was reported to be overexpressed in esophageal cancer with a poor prognosis. The purpose of the present study was to examined Mina53 expression and its relationship to clinicopathological parameters in human renal cell carcinoma (RCC). Mina53 and Ki-67 expression was examined on immunohistochemistry for 64 surgically resected RCC and non-cancerous tissue. In addition, the relationship between Mina53 expression and clinicopathological prognostic factors of RCC such as age, stage, microvenous invasion (MVI), histological subtype, Ki-67 labeling index (LI), and prognosis, was examined. Mina53 was expressed in the nuclei of tumor cells and tubular nuclei of normal renal tissue. The expression level of Mina53 was significantly higher in patients with poor prognostic factors (stage IV, MVI-positive, and sarcomatoid RCC, and high Ki-67 LI). The prognosis of high Mina53-expressing tumors was significantly poorer than that of non-Mina53-high tumors (P < 0.0001). In conclusion, Mina53 is overexpressed in RCC tissue from patients with poor prognostic factors, suggesting that Mina53 overexpression is one of the factors for poor prognosis in RCC.

Growth inhibitory effects of IFN-beta on human liver cancer cells in vitro and in vivo.

We investigated the effects of interferon-beta (IFN-beta) on the growth of human liver cancer cells. The effects of IFN-beta with or without 5-fluorouracil (5-FU) on the proliferation of 13 liver cancer cell lines were investigated in vitro. Chronologic change in IFN-alpha receptor 2 (IFNAR-2) expression was monitored in hepatocellular carcinoma (HCC) cells (HAK-1B) cultured with IFN-beta. After HAK-1B cells were transplanted into nude mice, various doses of IFN-beta were administered, and the tumor volume, weight, histology, tumor blood vessel, and angiogenesis factor expression were examined. IFN-beta inhibited the growth of 11 cell lines with apoptosis in a dose-dependent and time-dependent manner. With IFN-beta, IFNAR-2 expression in HAK-1B cells was significantly downregulated from 6 to 12 h. IFN-beta induced a dose-dependent decrease in tumor volume and weight and a significant increase of apoptosis in the tumor. Both basic fibroblast growth factor (bFGF) and blood vessel number in the tumor decreased only in mice receiving the lowest dose (1000 IU) of IFN-beta. IFN-beta with 10 muM of 5-FU frequently induced synergistic antiproliferative effects. IFN-beta with or without 5-FU induces strong antitumor effects in HCC cells, and we conclude that IFN-beta is useful for the prevention and treatment of HCC.

Effects of IFN-alpha on alpha-fetoprotein expressions in hepatocellular carcinoma cells.

We investigated the effects of pegylated (PEG)-IFN-alpha2b on alpha-fetoprotein (AFP) expression as demonstrated by protein and mRNA levels in six human hepatocellular carcinoma (HCC) cell lines. The number of KIM-1 cells in culture with PEG-IFN-alpha2b decreased between 24 amd 240 h, whereas the levels of intracellular and secreted AFP per cellular protein increased (except at 192 h), with levels 1.9-fold and 2.9-fold higher at maximum, respectively, than cells without PEG-IFN-alpha2b (control). The mRNA level increased between 72 and 192 h, when the level was 3-fold higher than that of the control. In the 72-h culture with 40-5000 IU/mL PEG-IFN-alpha2b, there were dose-dependent increases in AFP protein and mRNA expression and dose-dependent decrease in cell number resulting from apoptosis and blockage of the cell cycle at the S-phase. The rate of fucosylated AFP in the cell lysate decreased in a dose-dependent and time-dependent manner. In the PEG-IFN-alpha2b culture of the other five HCC cell lines, cell proliferation was suppressed, but the expressions of AFP protein and mRNA increased in only two cell lines, and suppression of cell proliferation was not related to the increase in AFP expressions. Our findings demonstrated that PEG-IFN-alpha2b induces an increase in AFP expression at both the protein and mRNA levels.

Autopsy case of disseminated Trichosporon inkin infection identified with molecular biological and biochemical methods.

Trichosporon species are usually opportunistic pathogens. Disseminated trichosporonosis is uncommon but is increasingly reported with a high mortality rate, especially in immunocompromised patients. Although Trichosporon asahii and T. mucoides are known as the most common pathogens of disseminated trichosporonosis, cases of systemic infection due to T. inkin have been reported recently. However, no autopsy case of disseminated T. inkin infection has been reported. Herein is presented an autopsy case of disseminated trichosporonosis caused by T. inkin in a 30-year-old man with allogenic peripheral blood stem cell transplantation for acute myelocytic leukemia. In the present case, identification of T. inkin was performed with morphological, molecular biological and biochemical methods. It is difficult to make a diagnosis of Trichosporon infection on only histological examination; therefore, molecular biological and biochemical methods are needed in a diagnosis of disseminated trichosporonosis.

Reinstatement of "germinal epithelium" of the ovary.

BACKGROUND: The existing dogma that the former term ovarian "germinal epithelium" resulted from a mistaken belief that it could give rise to new germ cells is now strongly challenged. DISCUSSION: Two years ago, a research group of the University of Tennessee led by Antonin Bukovsky successfully demonstrated the oogenic process from the human ovarian covering epithelium now commonly called the ovarian surface epithelium. They showed the new oocyte with zona pellucida and granulosa cells, both originated from the surface epithelium arising from mesenchymal cells in the tunica albuginea, and stressed that the human ovary could form primary follicles throughout the reproductive period. This gives a big impact not only to the field of reproductive medicine, but also to the oncologic area. The surface epithelium is regarded as the major source of ovarian cancers, and most of the neoplasms exhibit the histology resembling müllerian epithelia. Since the differentiating capability of the surface epithelium has now expanded, the histologic range of the neoplasms in this category may extend to include both germ cell tumors and sex cord-stromal cell tumors. SUMMARY: Since the oogenic capability of ovarian surface cells has been proven, it is now believed that the oocytes can originate from them. The term "germinal epithelium", hence, might reasonably be reinstated.

Antiproliferative effects of 5-fluorouracil and interferon-alpha in combination on a hepatocellular carcinoma cell line in vitro and in vivo.

BACKGROUND AND AIM: We investigated the antiproliferative effects of interferon-alpha (IFN-alpha) and 5-fluorouracil (5-FU) in combination on a hepatocellular carcinoma (HCC) cell line. METHOD: In the in vitro study, IFN-alpha and/or 5-FU was added to the culture of the poorly differentiated-type HCC cell line, HAK-1B, and their antiproliferative effects and additional or synergic effects in combination treatment were examined. In the in vivo study, HAK-1B cells were transplanted into nude mice and the changes in tumor volume and weight, apoptosis, BrdU and cyclin A positive cells, and artery-like blood vessels were investigated. Expressions of angiogenesis factors and IFN-alpha receptor (IFNAR-2) were examined in the developed tumors. RESULTS: In vitro growth of HAK-1B cells was suppressed dose-dependently to 5-FU, but the addition of IFN-alpha did not induce additional or synergic effects. In vivo growth in terms of tumor diameter and weight was suppressed at most in the IFN-alpha + 5-FU (combination) group, that is, the tumor volume became 29.3% and the tumor weight became 54.7% of the control. In the combination group, numbers of BrdU-positive S-phase cells and cyclin A positive cells increased together with the increase in apoptotic cells, but there was no significant relation between the tumor shrinkage effects and angiogenesis factors or artery-like blood vessels. In the combination group, INFAR-2 decreased significantly in comparison to the other groups. CONCLUSION: The synergic growth-suppression effects in the current in vivo study using the combination treatment are attributable to the enhanced induction of S-phase arrest and of apoptosis.

Expression of vascular endothelial growth factor-C in human hepatocellular carcinoma.

BACKGROUND/AIMS: Vascular endothelial growth factor-C (VEGF-C) is thought to be an important factor in tumor angiogenesis/lymphangiogenesis, but its role in hepatocellular carcinoma (HCC) has not yet been fully investigated. METHODS: We immunohistochemically examined VEGF-C expression in surgically resected tissues of 90 HCC. RESULTS: In the 78 HCC with a single histological grade, VEGF-C expression was significantly stronger in poorly differentiated HCC than in well- (P=0.003) or moderately differentiated HCC (P=0.0002). A 'nodule-in-nodule' case presented VEGF-A expression in the well-differentiated component and VEGF-C expression in the moderately-poorly differentiated component. According to nodular diameter, VEGF-C expression was significantly higher in nodules of 3.0 cm or larger (P=0.0263). Extrahepatic metastases seen in seven cases expressed VEGF-C. In 20 of the 28 cases who were able to be followed up, the frequency of intrahepatic recurrence tended to be higher and extrahepatic metastasis was significantly higher in the cases who had VEGF-C expression in the tumor casts of the intrahepatic portal/hepatic vein branches than other cases without the expression (P=0.0139). Disease-free survival time tended to be shorter in cases with VEGF-C expression in tumor casts of the portal/hepatic vein than in those without VEGF-C expression (P=0.053; log-rank test). CONCLUSIONS: VEGF-C expression is related to the progression of HCC, and VEGF-C expression in tumor casts of the intrahepatic portal/hepatic vein is considered to be a factor indicating recurrence/metastasis sites.

Angiogenesis in cancer.

New growth in the vascular network is important since the proliferation, as well as metastatic spread, of cancer cells depends on an adequate supply of oxygen and nutrients and the removal of waste products. New blood and lymphatic vessels form through processes called angiogenesis and lymphangiogenesis, respectively. Angiogenesis is regulated by both activator and inhibitor molecules. More than a dozen different proteins have been identified as angiogenic activators and inhibitors. Levels of expression of angiogenic factors reflect the aggressiveness of tumor cells. The discovery of angiogenic inhibitors should help to reduce both morbidity and mortality from carcinomas. Thousands of patients have received antiangiogenic therapy to date. Despite their theoretical efficacy, antiangiogeic treatments have not proved beneficial in terms of long-term survival. There is an urgent need for a new comprehensive treatment strategy combining antiangiogenic agents with conventional cytoreductive treatments in the control of cancer.

Expression and activation of apoptosis-related molecules involved in interferon-alpha-mediated apoptosis in human liver cancer cells.

Interferon (IFN)-alpha directly inhibits proliferation of liver cancer cells by inducing apoptosis, but the molecular mechanisms by which IFN-alpha induces apoptosis in these cells are not fully understood. We examined the effect of broad spectrum caspase inhibitor, Z-VAD-fmk, and the caspase activation in IFN-alpha-mediated apoptosis by using 4 liver cancer cell lines that were sensitive or resistant to IFN-alpha-mediated apoptosis. Involvement of apoptosis-related mitochondrial proteins and Bcl-2 family proteins in IFN-alpha-mediated apoptosis was further examined in 1 sensitive cell line (KIM-1). The Z-VAD-fmk completely or moderately inhibited IFN-alpha-mediated apoptosis in the sensitive cells. IFN-alpha induced time-dependent activation of caspase-3 in the sensitive cells, while the resistant cells showed mild or no activation. Activation of caspase-9, caspase-8, and caspase-7, and the cleavage of poly(ADP-ribose)polymerase were identified in either or both of the sensitive cell lines, but not in the resistant cells. In KIM-1 cells, the release of cytochrome c and Smac/DIABLO from mitochondria to cytosole was confirmed. Meanwhile, Bcl-xL was upregulated, and Bid activation or translocation, or conformational changes of Bax were not identified. In conclusion, our results suggest IFN-alpha-mediated apoptosis in liver cancer cells involves the mitochondrial apoptotic pathway and is induced by activating various caspases.

Expression of matrix metalloproteinases (MMPs) in cultured hepatocellular carcinoma (HCC) cells and surgically resected HCC tissues.

Matrix metalloproteinases (MMPs) relate to the growth and infiltration of cancer cells, but the frequency and amount of their expression are not yet fully examined in hepatocellular carcinoma. Expression of MMPs (MMP-2, MMP-7, MMP-9, MT1-MMP, MT2-MMP, MT3-MMP) and tissue inhibitors of metalloproteinase (TIMP: TIMP-1, TIMP-2) was investigated on cultured hepatocellular carcinoma (HCC) cells and surgically resected HCC tissues. The cultured cells and tissues expressed MMPs and TIMPs at various degrees, and high expression was observed for MMP-2, MMP-9, MT1-MMP and TIMP-2. Expression of MMP-7, MT2-MMP and TIMP-1 was found at a low frequency and a low amount in both the cells and the tissues. MMP-2 was expressed in various cells: HCC cells, vascular wall and sinusoidal endothelial cells in the cancer area of surgically resected tissues; and hepatocytes, bile duct cells, vascular wall, macrophages and Kupffer cells in the non-cancerous area. MMPs and TIMPs were expressed at a relatively high frequency in hepatocytes of the cancerous area and surrounding non-cancerous area as well as in the other cells and tissues. MMPs and TIMPs may be involved in the progression of hepatocellular carcinoma including the infiltration of cancer cells.