Well-differentiated Type Research Articles

Modified Classification of MRI Findings to Predict Histologic Grading of Liposarcomas

Purpose: To predict the histopathologic grading of liposarcomas with the modified classification of MRI findings. Materials and Methods: The 47 MRI studies of pathologically confirmed liposarcomas were retrospectively analyzed, and found to have well-differentiated (n=17) and myxoid (n=16) types, representing the 'low grade' sarcomas, as well as the round cell (n=9) and pleomorphic (n=5) types, which represent the 'high grade' sarcomas. The MRI findings of liposarcomas were classified into four groups as the one with fat signal above 80%, 20-80%, below 20%, and no fat signal on T1-weighted images (WIs), into three groups as the one with high signals with reticular or irregular lines, homogeneous above 50% of the area, and heterogeneous above 50% on the T2WIs, and into three groups as the one enhanced with reticular or irregular lines and enhancement areas above 50% and below 50% on the Gd-DTPA T1WIs. Results: The sarcomas with a lower amount of fat signals on T1WIs had a significantly higher histologic grade (p = 0.026) and also showed heterogeneous high signals above 50% on the T2WIs was statistically significant difference (p = 0.010) but not on the contrast enhanced T1WIs (p = 0.070). Conclusion: The modified classification of the MR findings could help predict the histologic grading of liposarcomas.

Poorly Differentiated Squamous Cell Carcinoma Arising in Tattooed Skin

Introduction. Tattoos have increasingly become accepted by mainstream Western society. As a result, the incidence of tattoo-associated dermatoses is on the rise. The presence of a poorly differentiated squamous cell carcinoma in an old tattooed skin is of interest as it has not been previously documented. Case Presentation. A 79-year-old white homeless man of European descent presented to the dermatology clinic with a painless raised nodule on his left forearm arising in a tattooed area. A biopsy of the lesion revealed a poorly differentiated squamous cell carcinoma infiltrating into a tattoo. The lesion was completely excised and the patient remains disease-free one year later. Conclusion. All previous reports of squamous cell carcinomas arising in tattoos have been well-differentiated low-grade type or keratoacanthoma-type and are considered to be coincidental rather than related to any carcinogenic effect of the tattoo pigments. Tattoo-associated poorly differentiated invasive carcinoma appears to be extremely rare.

Identification of Makorin 1 as a novel SEREX antigen of esophageal squamous cell carcinoma

BackgroundEsophageal squamous cell carcinoma (SCC) represents one of the most malignant tumors. To improve the poor prognosis, it is necessary to diagnose esophageal SCC at early stages using new tumor markers. SEREX (serological identification of antigens by recombinant cDNA expression cloning) is suitable for large-scale screening of tumor antigens and has been applied for various types of human tumors.MethodsTumor markers of esophageal squamous cell carcinoma (SCC) were screened by SEREX method. The presence of serum anti-makorin 1 (MKRN1) antibodies (s-MKRN1-Abs) was examined by Western blotting using bacterially expressed MKRN1 protein. The expression levels of MKRN1 mRNA in tissues were examined by RT-PCR. The biological activity of MKRN1 was examined by transfection of ras-NIH3T3 mouse fibroblasts with MKRN1 cDNA. Major ubiquitinated proteins in MKRN1-transfected cells were identified by immunoprecipitation with anti-ubiquitin antibody followed by mass spectrometry.ResultsMKRN1 was identified as a novel SEREX antigen of esophageal SCC. Although a total of 18 (25%) of 73 patients with esophageal SCC had s-MKRN1-Abs, none of the 43 healthy donors had a detectable level of s-MKRN1-Abs. There was no correlation between the presence of s-MKRN1-Abs and clinicopathological variables other than histological grading. Well-differentiated tumors were associated significantly with the presence of s-MKRN1-Abs in the patients. The mRNA levels of MKRN1 were frequently higher in esophageal SCC tissues than in the peripheral normal esophageal mucosa. Stable transfection of ras-NIH3T3 cells with MKRN1 cDNA induced prominent morphological changes such as enlargement of the cell body and spreading. Ubiquitination of 80- and 82-kDa proteins were clearly observed in MKRN1-transfected cells but not in the parental cells, which were identified as L-FILIP (filamin A interacting protein 1).ConclusionMKRN1 is a novel SEREX antigen of esophageal SCC, and s-NKRN1-Abs can be a candidate of diagnostic markers of esophageal SCC with high specificity. It is plausible that MKRN1 is involved in carcinogenesis of the well-differentiated type of tumors possibly via ubiquitination of L-FILIP.

Index of Suspicion in the Nursery

A 4-day-old term female infant is being evaluated for fever, with a rectal temperature of 100.9°F (38.2°C), and an episode of oxygen desaturation to 70% while breathing room air. The mother reports that the infant had increasing fussiness. Prenatal care and delivery were within normal parameters. She denies use of illicit drugs and is unsure of her group B Streptococcus status. The infant has eight to nine wet diapers and about 10 bowel movements per day. She consumes 1 to 2 oz of regular infant formula every 3 hours. The only finding of note on physical examination is the fever. Her neck is supple and has no abnormalities. A full sepsis evaluation is performed, including a complete blood count and blood, urine, and cerebrospinal fluid cultures. Respiratory syncytial virus antigen and influenza test results are negative. Radiographs of the chest and lungs appear normal. The infant is admitted and treatment with ampicillin and cefotaxime is begun. Thirteen hours later, the infant develops respiratory distress manifesting with stridor and desaturation while breathing room air. Physical examination at this time reveals a new cystic, moveable mass on the anterior triangle of her neck. Follow-up radiograph of the neck shows displacement of the trachea to the right. An 80% helium/20% oxygen mixture is started in the pediatric intensive care unit. Computed tomography (CT) scan of the neck and chest shows a 4.0×2.5-cm cystic lesion with an air-fluid level located in the anterior triangle of her neck slightly to the left of midline (Fig. 1). Thyroid study results are normal. Surgical removal of the cyst and histologic evaluation lead to the diagnosis. Figure 1. Computed tomography scan showing a cystic lesion with an air-fluid level in the anterior triangle of the neck. ### Hospital Course The patient was taken to the operating room the next day for neck exploration. …

Synchronous bilateral mucinous carcinoma of the breast: case report

A mucinous carcinoma of the breast is a well-differentiated rare histological type of invasive ductal carcinoma, having a lower frequency of metastasis to an axillary lymph node and a better survival rate. Bilateral breast cancer has an overall incidence of 4% to 20% in patients with primary operable breast cancer. Few reports exist in the clinical literature characterizing a synchronous bilateral mucinous carcinoma of the breast. We report the characteristic imaging findings of a bilateral mucinous carcinoma of the breast.

Epidemiology of Squamous Cell Carcinoma of the Oral Cavity in Iran

Squamous cell carcinoma accounts for approximately 90% of oral malignancies. This study was performed to determine the prevalence of oral squamous cell carcinoma (OSCC) in southern Iran in relation to sex, age, subsite distribution, and histologic differentiation of the tumor. Pathologic records of patients with a histologic diagnosis of OSCC at Fars Cancer Registry of Nemazee Hospital affiliated to Shiraz University of Medical Sciences during the period of April 1992 through March 2007 were reviewed. Among 11,220 cases of cancer registered during this period, 200 cases were OSCC (1.7%). The age range of patients was 4 to 87 years (mean, 56.9 years; SD, 15.5 years), with a 1.4:1 male-female ratio. Oral squamous cell carcinoma occurred more frequently in patients older than 60 years. The tongue was the most commonly affected site (53%), followed by the buccal mucosa (9.5%) and maxillary gingiva (9%). The well-differentiated type (55.5%) was the most common, with the poorly differentiated OSCC being the least common (7.5%). The present study showed that OSCC was the most common malignancy in the tongue and buccal mucosa being more common in older age and male sex.

Knowledge Helps, but Alone It Is Not Enough

To the Editor: The understanding of soft tissue sarcoma has progressed impressively in the last two decades. Delineation of the biology, molecular diagnosis, and outcome have been carefully characterized with defined prognostic indicators. The challenge has been to identify if biology can predict behavior; that has now been clearly established. More importantly, can biology and predictive outcome mandate treatment change, and finally can treatment, based on biology and known outcome, be altered to reflect improved outcome? Dr Pollock and his coauthors examine this question by defining retroperitoneal liposarcoma into well-differentiated (WD) and dedifferentiated (DD) subtypes.1 They examined 135 patients over the last 10 years at their institution. This significant experience in a major sarcoma center allows important observations. As expected, WD was mostly primary and DD was mostly recurrent. Chemotherapy was rarely used in WD, and more aggressive resection was required in DD, while a third to half of all patients required multivisceral resection. The initial complete gross resection was obtained in both groups, and, as expected, recurrence was greater in the dedifferentiated group. As previously identified, metastatic disease is rare in well-differentiated liposarcoma and local recurrence can be late and prolonged. While the title of the present manuscript, “Two Different Diseases Possibly Requiring Different Treatment Approaches,” is most enticing, the data predominantly confirm that accurate diagnosis of histological subtype predicts recurrence. A recent nomogram based on 800 patients with liposarcoma has confirmed the importance of histological subtype.1 Few would challenge the authors questioning of whether, with such different outcomes, treatment should be different; however, how different is different? The real challenge, alluded to in the title, is what “different” treatment should be applied to these “different” diseases. The authors are clearly aware of the different outcomes, and that has already affected management. In both groups radiation is minimally used (<20%), whereas chemotherapy is essentially never used in the well-differentiated type and used in the dedifferentiated type in the majority (73%). However, the benefits of such different approaches are unclear. Despite aggressive use of multimodality therapy, outcome remains poor with 5-year survival in DD at 37%. This is similar to that reported by Dalal et al. at 39%.2 Unfortunately, the real challenge remains; we can increasingly improve the accuracy of histological diagnosis, molecular characterization, and prediction of outcome, but we are far less sanguine about improvements in treatment that translate into better survival. Importantly, the reverse is true. We are now aware that we can diminish the aggressivity of surgical approaches when the biology is favorable and the consequence of recurrence limited. The authors confirm that less aggressive surgical approaches for WD are appropriate. The presence of WD liposarcoma especially an asymptomatic locally recurrent lesion does not mandate operation! It is fortunate that our knowledge increases and unfortunate that we cannot transfer that increase of knowledge into more effective therapy. We take some consolation in the fact that we can decrease morbidity of surgical therapy by better understanding of biology.

Multiple gastric endocrine tumours and gastrinomas of the duodenum in a patient with ZES MEN 1

An asymptomatic 39-year-old man, coming from a family aving a genetic nonsense mutation (type Arg415Stop, exon ) for multiple endocrine neoplasia type 1 (MEN 1), was een in our Unit to undergo screening tests, because he was carrier of the same mutation. Laboratory evaluation revealed high levels of gasrin (41,400 pg/ml, nv 20–100 pg/ml), chromogranin (17,000 U/l, nv <17 U/l), calcium (12.9 mg/dl, nv –11.5 mg/dl) and parathyroid hormone (325 pg/ml, nv 4–72 pg/ml). The patient underwent upper-gastrointestinal endoscopy hich revealed, in the gastric body and fundus (Fig. 1), ultiple polyps which involved almost the entire mucosa. e did not find any lesions in the antrum. The gastric olyps varied from 1–2 mm to 3 cm. In addition, in the econd portion of the duodenum, there were sessile polyps hich varied from 1 cm to 3 cm (Fig. 2). The gastric pH as 1.5. Pathological examination of multiple biopsy pecimens showed a well-differentiated endocrine tumour gastric carcinoid type II: chromogranin positive and gastrin egative) in the stomach and a well-differentiated gastrinroducing endocrine tumour of the duodenum (gastrinoma). his diffuse gastric carcinoidosis is the consequence f the trophic effect on the entero-chromaffin-like cells ECL) of the gastric body and fundus induced by gastrin ecreted by the duodenal gastrinomas in a patient with ZES EN 1.

Pancreaticoduodenectomy for advanced gastric cancer with pancreaticoduodenal region involvement

To characterize the factors of the improved survival following combined pancreaticoduodenectomy (PD) and gastrectomy for the treatment of advanced gastric cancer with pancreaticoduodenal region involvement. From 1995 to 2004, 53 patients with primary gastric cancer were diagnosed with synchronous (n = 44) or metachronous (n = 9) pancreaticoduodenal region involvement. Of these, 17 patients (32%) underwent total gastrectomy (TG) or distal subtotal gastrectomy (SG) combined with PD simultaneously. The preoperative demographic, clinical information, clinicopathologic features and the surgical results of these 17 patients were considered as factors influencing survival and were analyzed by the Kaplan-Meier method with log-rank comparison. The actual 1- and 3-year survival rates of these 17 patients after resection were 77% and 34%, respectively, and three patients survived for more than 5 years after surgery. The tumor-free resection margin (P = 0.0174) and a well-differentiated histologic type (P = 0.0011) were significant prognostic factors on univariate analysis. No mortality occurred within one mo after operation, postoperative weight loss of different degree was present in all the patients with TG and 12 cases had other complications. There were 9 (53%) cases of recurrence in 5-48 mo after operation. The survival rate in the palliative and explorative group was significantly (P = 0.0064) lower than in the combined PD group. Judicious use of en bloc PD and gastrectomy and strictly preventing postoperative complications may improve the long-term survival for advanced gastric cancer patients with pancreaticoduodenal region involvement. Well-differentiated histology and negative resection margin are the most important predictors of long survival.

口腔に発生した脂肪肉腫の２例

Liposarcoma is a malignant tumor of the soft tissues, but it is extremely rare in the oral cavity, particularly in the tongue. The tumor typically presents as a painless, slowly enlarging mass, and wide surgical excision is important for successful management. We describe 2 patients with liposarcoma involving the tongue and buccal region, with reference to the existing literature.Patient 1 was a 60-year-old woman with a mass arising in the right inferior surface of the tongue. The suspected clinical diagnosis was lipoma of the tongue. Patient 2 was a 42-year-old man with swelling of the right cheek. The suspected clinical diagnosis was pleomorphic adenoma of the buccal region. Tumor excision followed by rapid intraoperative pathological examination in both patients revealed no apparent malignancy. However, the postoperative histopathological diagnosis was well-differentiated liposarcoma in patient 1 and well-differentiated type liposarcoma with metaplastic bone formation in patient 2. We thus surgically excised the tumor with a wide safety margin in patient 1 and applied postoperative radiotherapy to the buccal cheek in patient 2. Both patients remain free of reccurence and metastasis.These findings show that low-grade well-differentiated liposarcoma can be difficult to distinguish from other types of lipoma.

Gastric Cancer Risk and Erythrocyte Composition of Docosahexaenoic Acid with Anti-inflammatory Effects

Infection with Helicobacter pylori is linked to inflammation and is the main cause of peptic ulcer, gastritis, and gastric malignancies. To examine associations between gastric cancer risk and the erythrocyte composition of docosahexaenoic acid (DHA), a fatty acid with anti-inflammatory and apoptosis-inducing effects, here we conducted a case-control study of 179 incident gastric cancer cases and 357 noncancer controls (matched by age, sex, and season of sample collection). Dietary information and blood samples were collected from all subjects, and erythrocyte fatty acid levels were measured using accelerated solvent extraction and gas-liquid chromatography. Gastric cancer risk did not seem to be directly associated with dietary intake of fish and n-3 highly unsaturated fatty acids (HUFAs), such as DHA, derived from fish. However, risk was inversely associated with erythrocyte compositions of n-3 HUFAs [the highest to the lowest tertile, odds ratio (OR), 0.39; 95% confidence interval (95% CI), 0.23-0.68; P(trend)<0.005] and DHA (OR, 0.47; 95% CI, 0.28-0.79; P(trend)<0.01). Particularly strong associations were noted for well-differentiated type lesions and n-3 HUFAs (OR, 0.10; 95% CI, 0.03-0.35; P(trend)=0.0005) as well as DHA (OR, 0.20; 95% CI, 0.07-0.58; P(trend)<0.01) values. In conclusion, the erythrocyte composition of DHA was found to be negatively linked to risk of gastric cancer, especially of well-differentiated adenocarcinoma. Further studies are needed to investigate mechanisms of action of DHA relevant to antitumor effects in the stomach.

Expression and roles of keratinocyte growth factor and its receptor in esophageal cancer cells

The keratinocyte growth factor receptor (KGFR), also known as FGFR2 IIIb, is mainly localized in epithelial cells and is activated by the keratinocyte growth factor (KGF) that is predominantly synthesized by mesenchymal cells. In this study, we examined the roles of KGFR and KGF in human esophageal cancer (EC). In noncancerous esophageal tissues, KGFR was localized in epithelial cells from the basal region of the epithelium to the lower one-third of the epithelium, and KGF was weakly localized in the basal to parabasal epithelial cells. On the other hand, Ki-67 was localized in the parabasal cells. In EC tissues, KGFR and KGF were expressed in cancer cells in 22 and 37 of 54 patients, respectively. The coexpression of KGFR and KGF in cancer cells was detected in 14 of 54 (26%) patients. Clinicopathologically, KGFR expression correlated with the well-differentiated cell type of EC (p<0.001), and KGF expression correlated with lymphatic invasion and lymph node metastasis (p=0.004 and 0.021, respectively). The coexpression of KGFR and KGF in cancer cells correlated with the well-differentiated cell type of EC (p=0.001). KGFR-positive, KGF-positive and KGFR/KGF coexpression patients tended to have shorter survival rates, but the survival rates were not statistically significantly different (p=0.44, 0.059 and 0.112, respectively). In human EC cell lines (TE-1, TE-8 and TE-11), KGFR mRNA was expressed but no KGF mRNA was detected. The KGFR mRNA level was highest in TE-1 cells, derived from well-differentiated SCC and lowest in TE-8 cells. KGFR was detected in the cancer cell lines by Western blot analysis. Recombinant human KGF significantly stimulated the growth of TE-8 and -11 cells, derived from moderately differentiated SCC, but had no effect on TE-1 cell growth. These results suggest that KGFR expression correlates with the differentiation of a normal esophageal epithelium and the well-differentiated cell type of EC. On the other hand, KGF may induce the growth of some EC cells in a paracrine manner and closely correlates with lymphatic invasion and lymph node metastasis.

The impact of large sections on the study of in situ and invasive duct carcinoma of the breast

Large histologic sections (LHSs) are increasingly used in the study of normal and neoplastic breast tissue. LHSs allow the direct visualization of a large part of the breast glandular tree. Accordingly, LHSs have shown that in situ and invasive lobular carcinoma is a multilobar (and hence multifocal) neoplastic lesion in more than 50% of the cases, and that poorly differentiated duct carcinoma in situ (DCIS grade 3) is frequently unifocal, whereas it is often multifocal when the in situ lesion is a well-differentiated type (DCIS grade 1). Forty-five mastectomies were studied with large sections. Mastectomies were performed when quadrantectomy did not guarantee radical excision of the tumor with adequate cosmesis because of the large size of the lesion or because the neoplastic lesion was located below the nipple. Excluded were cases of lobular neoplasia or invasive lobular carcinoma, because they were reported separately, and cases of mastectomies performed for sarcoma or recurrent phyllodes tumor. All cases had undergone a preoperative diagnostic procedure (fine needle aspiration), and the relative positive material was reviewed. All 45 cases showed in situ duct carcinoma and 37 showed evidence of invasive duct carcinoma. Forty-two cases of DCIS were multifocal, whereas only 4 invasive duct carcinoma were shown as multifocal. When DCIS lesions were subdivided into 3 grades, no statistical significance was seen among the 3 groups of DCIS in regard to multifocality. Nevertheless, DCIS grade 1 was a widespread condition involving more than one lobe and quadrant, whereas DCIS grades 2 and 3 appeared more localized. DCIS grade 1 was more similar to that previously observed in lobular in situ neoplasia/lobular in situ carcinoma. In 66.6% of the cases, DCIS foci were found within the invasive areas, indicating a more than fortuitous occurrence (2-sided P=.0357).

Efficacy of NBI System for the Diagnosis of the Lateral Extension of Superficial Gastric Cancer

Background: The diagnosis of lateral extension of superficial gastric cancer is sometimes difficult when the color and surface pattern was close to surrounding mucosa. Narrow Banding Image (NBI) is a novel endoscopy system that enables to observe the lesions more precise. However, the effectiveness for the diagnosis of lateral extension was obscure. The aim of this study is to clarify the usefulness of NBI system for the diagnosis of lateral extension of superficial gastric cancer. Patient and method: One hundred patients those had superficial gastric adenocarcinoma, well-differentiated type, were undergone to this study prospectively from Sep.

Gingival liposarcoma: An unusual polyp

Liposarcomas account for up to 20% of all soft tissue tumours. They are uncommon in the head and neck. Sarcomas of the oral region (excluding lymphoma) account for 5% of all oral cancers, of which 10% are liposarcomas. Fewer than 80 cases have been reported in the world literature, most of which presented as expansile masses. The prognosis of liposarcoma is dependant on the histopathologic type, location, and adequacy of surgical treatment. Well-differentiated types have a good prognosis and minimal metastatic potential. We report a case of well-differentiated liposarcoma (lipoma-like subtype), that presented as a gingival polyp.

Concomitant hepatocellular carcinoma and non‐Hodgkin's lymphoma in a patient with nodular regenerative hyperplasia

Hepatocellular carcinoma (HCC) is the most common primary cancer in the liver. Liver invasion of non-Hodgkin's lymphoma (NHL) is also often observed. But simultaneous existence of HCC and NHL in a liver is extremely rare. Such patients reported previously had cirrhotic livers. Herein is reported a patient who simultaneously had HCC and NHL in a liver without cirrhosis, but with nodular regenerative hyperplasia (NRH). NHL was of the diffuse large B-cell type. Lymphoma cells invaded the portal vein, and formed thrombi. These thrombi would contribute to the development of NRH by decreasing portal vein blood flow. HCC was of the well-differentiated type and there was a 2 cm-sized nodule at the lateral segment. There is the possibility that NRH was associated with the HCC because NRH is reported as a premalignant lesion. HCC and NHL were colocalized in the liver without hepatic virus infection or cirrhosis, although common cause(s) of development of these malignancies remain unclear in the present case.

PET evaluation of fatty tumors in the extremity: Possibility of using the standardized uptake value (SUV) to differentiate benign tumors from liposarcoma

The relative utility of various preoperative diagnostic imaging modalities, including PET (utilizing FDG and FMT), CT, and MR imaging, for evaluation of lipoma and liposarcoma, especially well-differentiated liposarcoma, was investigated. Imaging findings in 32 patients with histopathologically documented lipoma, including one with fibrolipoma and one with angiolipoma, and 25 patients with liposarcomas whose subtypes included 10 well-differentiated, 10 myxoid, and 5 other types were reviewed retrospectively. Pre-operative imaging included FDG-PET (n = 44), FMT-PET (n = 21), CT (n = 25), and MR imaging (n = 53). Statistically significant imaging features of MR images favoring a diagnosis of liposarcoma involved lesions containing less than 75% fat (p < 0.001) as well as the presence of septa (p < 0.001). As compared with well-differentiated liposarcoma, benign lesions were differentiated significantly only by the presence of septa (p < 0.001), which also provided significant differentiation on CT (p < 0.05). The mean SUVs for malignant tumors were significantly higher than those for benign lesions in both FDG- and FMT-PET analyses (p < 0.0001, p = 0.0011, respectively). By using a cut-off value for FDG- and FMT-PET set at 0.81 and 1.0 respectively, which provided the highest accuracy, benign lesions were differentiated significantly from liposarcomas (p < 0.001, and p < 0.02). Furthermore, benign tumors and the three subtypes of liposarcoma were divided significantly into four biological grades by FDG- and FMT-accumulation rates (rho = 0.793, p < 0.0001; and rho = 0.745, p = 0.0009, respectively). A cut-off value of 0.81 for FDG-PET provided significant differentiation between benign lesions and well-differentiated liposarcoma (p < 0.01). The presence of septa on MR images differentiated lipomas from liposarcoma, even well-differentiated type. PET analysis, especially FDG-PET, quantitatively provided not only the differentiation but also the metabolic separation among subtypes of liposarcoma. Interpretation of the visual diagnostic modalities requires extensive experience and carries a risk of ignoring a critical portion of malignancy. PET metabolic imaging may be an objective and useful modality for evaluating adipose tissue tumors preoperatively.

Evaluation of Extracellular Signal Regulated Kinase Expression and Its Relation to Treatment of Hepatocellular Carcinoma

The aim of this study was to evaluate hepatocellular carcinoma (HCC) using a combination of extracellular signal regulated kinase (ERK) and other markers related to hepatocyte growth factor (HGF) in tumor tissue. Using specimens from 30 hepatocellular carcinoma patients operated on in our department from 2002 to 2003, we evaluated expression levels of HGF, c-Met, ERK, and cyclin D1 by Western blot. Expression levels of ERK and cyclin D1 proteins were significantly higher in patients with less well-differentiated type tumors by histologic examination or the presence of intrahepatic metastasis (IM). ERK expression in tumor tissue significantly correlated with both tumor size (p=0.0017, R(2)=0.355) and serum levels of HGF (p=0.0247, R(2)=0.218). Nontumor tissue level of cyclin D1 was significantly higher in patients with poor liver function (p=0.047). In patients with higher expression of ERK in tumor tissue compared with nontumor tissue, the histologic finding was more progressed; but a similar tendency was not observed for cyclin D1. In patients with overexpression of HGF and c-Met, the expression level of ERK was significantly higher, but cyclin D1 expression was not. The detected level of cyclin D1 was significantly higher in patients with overexpressed ERK in tumor tissue. Values of ERK and c-Met were correlated, and IM presence was detected more frequently in patients with high expression of ERK and c-Met protein. Even after complete removal of visible IM tumor, recurrence tumors were detected within 6 months in 7 patients with high expressions of both ERK and c-Met protein. Combination study of tumor expression of ERK might be useful to estimate the properties of hepatocellular carcinoma, especially for the presence of IM.

Squamous Cell Carcinoma of the Penis in a Man with a Human Papilloma Virus 31 Infection

We report a 51-year-old man with squamous cell carcinoma (SCC) on his penis. He was surgically treated for his phimosis when he was 20 years old. He presented with an indurated nodule on the tip of his penis. The tumor was treated with partial penectomy and standard inguinal lymphadenectomy. Histological examination revealed that the tumor was a well-differentiated type of SCC. A polymerase chain reaction was performed to detect human papilloma virus (HPV) DNA. The result revealed the presence of HPV in the SCC. The results of sequencing analysis showed that the DNA was HPV 31.

Screening of DNA copy‐number aberrations in gastric cancer cell lines by array‐based comparative genomic hybridization

We performed genome-wide screening for deoxyribonucleic acid copy-number aberrations in 31 gastric cancer (GC) cell lines by using custom-made comparative genomic hybridization (CGH)-array. Copy-number gains were frequently detected at 1q, 3q, 5p, 7p, 7q, 8q, 11q, 17q, 20p, 20q, Xp and Xq, and losses at 3p, 4p, 4q, 8p, 9p, 18p and 18q. With respect to histological subtypes, copy-number gains at 1p, 16p, 20p, 20q and 22q, and losses at 8p, 10p, 10q and 18q were significantly frequent in cell lines derived from tumors of the well-differentiated type, whereas copy-number gains at 1q, 7p, 7q, Xp and Xq were frequent in the undifferentiated type. Homozygous deletions were seen at five loci, whereas high-level amplifications were detected in 15 of the 31 GC cell lines; these had occurred at 24 loci, including the segment containing CDK6 (7q21.2). Amplification of that gene had never been reported in GC before. Immunohistochemical studies showed increased levels of CDK6 protein in 54 of the 292 primary GC samples we examined (18.5%). Cytoplasmic localization of CDK6, as well as CDK6 over-expression, was more frequent in well-differentiated GC than in undifferentiated tumors. Nuclear expression of CDK6 was more frequent in early stage GC than in advanced tumors, suggesting that nuclear localization of CDK6 is likely to be a prognostic factor for GC. Taken together, our data indicate that CDK6 might be involved in the pathogenesis of GC and, more generally, that CGH-arrays have a powerful potential for identifying novel cancer-related genetic changes in a variety of tumors.