Biomedical subjects

Hitoshi Tsuda

Publications and source records attributed to Hitoshi Tsuda.

At least 19 recordsLinked to original sources

PubMed2007

Effect of HER-2/neu overexpression on chemoresistance and prognosis in ovarian carcinoma.

AIM: To investigate the effect of HER-2/neu protein overexpression on chemoresistance and prognosis in patients with epithelial ovarian carcinoma. METHODS: A total of 141 ovarian carcinoma tissues surgically resected between 1987 and 2003 were assessed by immunohistochemistry (IHC). The characteristic of the patients and immunohistochemical results were compared by chi2-test. Survival analysis was performed by the Kaplan-Meier method and the log-rank test. RESULTS: HER-2/neu overexpression was detected in 18 cases (12.8%). There were no significant differences in histopathological subtypes (P = 0.3550), FIGO stages (P = 0.8858), or residual tumor size at first surgery (P = 0.6607) between the cases with HER-2/neu overexpression and the cases without HER-2/neu overexpression. Among the 58 cases which responded to chemotherapy, only five cases (8.6%) showed HER-2/neu overexpression. However, among the 38 cases which did not respond to chemotherapy, eight cases (21.1%) showed HER-2/neu overexpression. Overexpression of HER-2/neu had a tendency to relate with chemoresistance of epithelial ovarian carcinoma, but there were no statistically significant differences (P = 0.0817). No association was observed between HER-2/neu overexpression and cumulative survival rate (P = 0.4970). CONCLUSIONS: The results of the current study show that although HER-2/neu overexpression has a tendency to be associated with chemoresistance, it can not be a prognostic factor for the patients with epithelial ovarian carcinoma.

Adult↗

PubMed2006

Successful treatment of malignant pericardial effusion, using weekly paclitaxel, in a patient with breast cancer.

We report a case of metastatic breast cancer with pericardial effusion that was successfully treated with weekly paclitaxel. A 46-year-old woman underwent modified radical mastectomy in April 1997 and was readmitted to the hospital for dyspnea in March 2002. A diagnosis of cardiac tamponade due to breast cancer relapse was made, and the patient was treated with weekly paclitaxel (80 mg/m2) and insertion of a drainage catheter. This treatment was effective in preventing reaccumulation of the pericardial effusion until her death. The concentration of paclitaxel in the cardiac effusion was 45 ng/ml at 3 h, 15 ng/ml at 12 h, and less than 10 ng/ml at 24 h after paclitaxel infusion, indicating good transportation of the drug from the blood to the pericardial effusion. These findings suggest that weekly intravenous infusion of paclitaxel could be effective for the treatment of patients with malignant pericardial effusion.

Antineoplastic Agents, Phytogenic↗

PubMed2006

Tumor buds show reduced expression of laminin-5 gamma 2 chain in DNA mismatch repair deficient colorectal cancer.

PURPOSE: Tumor budding at the invasive margin of colorectal cancer is an important adverse prognostic factor. The subset of colorectal cancer that is deficient in DNA mismatch repair has been associated with a good prognosis. It is hypothesized that tumor budding in this subset may lack biologic aggressiveness because it is not associated with aberrant expression of the independent prognostic factor, laminin-5 gamma 2. METHODS: Eighty colorectal cancers with high-grade tumor budding were studied, including nine sporadic colorectal cancers with immunohistochemical loss of expression of MLH1 (MLH1(-)), seven colorectal cancers from patients with hereditary nonpolyposis colorectal cancer, and 64 sporadic colorectal cancers expressing both MLH1 and MSH2 (MLH1(+)). Two regulatory mechanisms for laminin-5 gamma 2 expression were explored, including aberrant nuclear expression of beta-catenin by immunohistochemistry and promoter methylation of laminin-5 gamma 2 by methylation-specific polymerase chain reaction. RESULTS: Only three of nine MLH1(-) colorectal cancers showed expression of laminin-5 gamma 2 compared with 46 of 64 MLH1(+) colorectal cancers (P = 0.05). Only two of seven hereditary nonpolyposis colorectal cancers expressed laminin-5 gamma 2 compared with MLH1(+) colorectal cancers (P= 0.03). Expression of nuclear beta-catenin was more frequent (58 percent) in MLH1(+) colorectal cancers compared with MLH1(-) colorectal cancers (11 percent, P = 0.01). Methylation of laminin-5 gamma 2 was found in 5 of 38 (13 percent) cases but did not differ among colorectal cancer subsets. Four of five colorectal cancers with methylation of laminin-5 gamma 2 were scored as negative for laminin-5 gamma 2 by immunohistochemistry. CONCLUSIONS: The reduced expression of laminin-5 gamma 2 in colorectal cancers with deficient DNA mismatch repair may underlie a variant of tumor budding that is relatively nonaggressive.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Differential prognostic significance of morphologic invasive markers in colorectal cancer: tumor budding and cytoplasmic podia.

PURPOSE: In colorectal cancer, the presence of cytoplasmic podia around tumor budding foci may be a morphologic marker for an activated budding phenotype that is associated with cell motility. In this study, we have investigated the prognostic significance of cytoplasmic podia. METHODS: A total of 136 pT3 colorectal cancers were classified according to extent of budding and cytoplasmic podia as identified by immunostaining for cytokeratin. The prognostic significance of budding and cytoplasmic podia was then assessed. RESULTS: The overall survival curves between the groups with high-grade and low-grade cytoplasmic podia were different (5-year survival rates were 60.5 and 83.8 percent respectively, P = 0.0003). Similar results were shown for tumor budding (59.8 and 87.7 percent, P < 0.0001). Multivariate analysis showed that the grades of cytoplasmic podia (hazards ratio, 2.4; P = 0.012) and budding (hazards ratio, 2.3; P = 0.024) were independent prognostic factors. Additionally, among colorectal cancers with high-grade budding, the grade of cytoplasmic podia was selected as an independent prognostic factor (hazards ratio, 2.4; P = 0.042). CONCLUSIONS: Cytoplasmic podia and budding are related but independent pathologic predictive markers in patients with resected pT3 colorectal cancer.

Aged↗

PubMed2006

Efficacy of accelerated partial breast irradiation as a neoadjuvant treatment for patients with breast cancer: a pilot study.

BACKGROUND: Breast conserving treatment (BCT) consists of breast-conserving operation and followed by whole-breast irradiation (WBI). Accelerated partial breast irradiation (APBI) is being considered as a possible alternative to WBI. Neoadjuvant APBI might provide more benefit than postsurgical APBI because tumor downstaging will enhance the likelihood of BCT. METHODS: APBI was delivered as 50 Gy in 5 fractions over 5 days before operation for patients with breast cancer of 3 to 4 cm in diameter. Patients with tumors 3 cm or less were deemed to be candidates for breast-conserving operation. RESULTS: Between September 1998 and August 1999, 12 women were enrolled. The mean tumor diameter and volume were reduced from 3.4 to 1.8 cm (reduction rate: 47%) and from 8.1 to 2.2 cm3 (reduction rate: 71%), respectively. The mean pathologic tumor size was 1.5 cm, and a complete pathologic response was found in 1 patient (8%). All patients were eligible for breast-conserving operation. No ipsilateral breast recurrences have been observed to date. CONCLUSIONS: This is the first report of neoadjuvant APBI for relatively large breast cancers. Although the number of participants was small, these results would encourage the development of clinical trials exploring the efficacy of neoadjuvant APBI.

Adult↗

PubMed2006

Potential crosstalk between insulin-like growth factor receptor type 1 and epidermal growth factor receptor in progression and metastasis of pancreatic cancer.

The insulin-like growth factor receptor type 1 (IGF1R) and epidermal growth factor receptor (EGFR) are reportedly overexpressed in pancreatic cancer. However, the correlation between activated EGFR and IGF1R and their clinicopathological implications still remain unclear. The cellular localization and overexpression of IGF1R and EGFR were investigated immunohistochemically in primary invasive ductal pancreatic carcinomas obtained from 74 patients who underwent radical surgical resection. We also compared the status of IGF1R and EGFR overexpression between primary tumors and hepatic metastatic tumors obtained from 44 autopsied patients. Among the 74 surgically resected primary tumors, cytoplasm- and membrane-dominant EGFR overexpression was detected in 22 (30%) and 7 (9%), respectively, whereas cytoplasm- and membrane-dominant IGF1R overexpression was detected in 8 (11%) and 28 (38%), respectively. Membrane-dominant EGFR and cytoplasm-dominant IGF1R were more frequent in lower-grade tumors and correlated with favorable prognosis, whereas cytoplasm-dominant EGFR and membrane-dominant IGF1R were more frequent in higher-grade tumors and correlated with poor prognosis. In 36 autopsy specimens of pancreatic tumor with concurrent overexpression of IGF1R and EGFR, there was an inverse correlation between the IGF1R and EGFR localization patterns (P = 0.001). In the hepatic metastatic tumors obtained by autopsy, the incidences of both IGF1R and EGFR overexpression were much higher than in the surgically resected primary tumors. More than half of the autopsy cases consistently showed membrane-dominant EGFR expression in both the primary tumor and hepatic metastases, whereas IGF1R expression showed considerable variation. Crosstalk between differently localized IGF1R and EGFR might play a role in determining the biological aggressiveness of pancreatic cancer, although their cellular localization may often alter during the process of metastasis.

Adenocarcinoma↗

PubMed2006

High-level Skp2 expression in pancreatic ductal adenocarcinoma: correlation with the extent of lymph node metastasis, higher histological grade, and poorer patient outcome.

OBJECTIVES: Recent studies have shown that overexpression of S-phase kinase-associated protein 2 (Skp2) occurs in many cancers at an advanced stage. We examined the clinicopathologic significance and prognostic implication of Skp2 expression in pancreatic invasive ductal carcinoma. METHODS: Tissue samples from 46 pancreatic carcinomas were examined immunohistochemically for Skp2. The proportion of constituent tumor cells with Skp2 expression was analyzed and classified as high-level nuclear expression when more than 20% of the cancer cells were positive, or low-level nuclear expression otherwise. RESULTS: High-level Skp2 overexpression was detected in 13 (28.3%) of the 46 tumors. The incidence of high-level Skp2 was correlated with higher histological grade (P = 0.0056), the extent of lymph node metastasis (P = 0.0086), the level of lymphatic permeation (P = 0.0024), and poorer patient outcome (P = 0.0189). Multivariate analysis showed that high-level Skp2 expression was an independent predictor of overall patient survival (P = 0.0140). CONCLUSIONS: It is suggested that examination of Skp2 expression might be clinically useful for prognostication in patients with pancreatic carcinoma and that Skp2 protein might be a novel therapeutic molecular target.

Adenocarcinoma↗

PubMed2006

Alternative tyrosine phosphorylation of signaling kinases according to hormone receptor status in breast cancer overexpressing the insulin-like growth factor receptor type 1.

The insulin-like growth factor receptor type 1 (IGF1R) is suggested to play important roles in cancer cell growth through cross-talk with hormone receptors and growth factor receptors. However, its clinical significance in breast cancers in vivo is still unclear. We examined immunohistochemically the expression of IGF1R, phosphorylated-AKT (pAKT) and phosphorylated-ERK1/2 (pERK1/2) using tissue microarray slides containing 150 cases of primary breast carcinoma. Their mutual correlation and correlation with the status of hormone receptors epidermal growth factor receptor and human epidermal growth factor receptor type 2 were also investigated. IGF1R overexpression was detected in 71 cases (47%), and was correlated with lower nuclear grade (P = 0.03), positive estrogen receptor (ER) and/or progesterone receptor status (P = 0.002). pERK1/2 expression, detected in 53 cases (35%), was correlated with positive ER (P < 0.0001) and lower nuclear grade (P = 0.014). pAKT expression, detected in 88 cases (59%), was not correlated with nuclear grade, hormone receptors status or other clinical parameters. Of the 71 IGF1R-overexpressing tumors, pERK1/2 expression was detected in 27 (56%) of 48 ER-positive cases but in only four (17%) of 23 ER-negative cases (P = 0.022). In contrast, pAKT expression was constantly (64% or higher) detected irrespective of hormone receptor status in IGF1R-overexpressing breast cancers. Taken together, these findings suggest that IGF1R overexpression might activate pERK1/2 and pAKT in hormone receptor-positive breast cancer, but activate only pAKT in hormone receptor-negative breast cancer.

Adult↗

PubMed2006

PIK3CA mutation is an oncogenic aberration at advanced stages of oral squamous cell carcinoma.

Phosphatidylinositol 3-kinases (PI3K) are a group of heterodimeric lipid kinases that regulate many cellular processes. Gene amplification and somatic mutations mainly within the helical (exon 9) and kinase (exon 20) domains of PIK3CA, which encode the 110-kDa catalytic subunit of PI3K and are mapped to 3q26, have been reported in various human cancers. Herein, 14 human oral squamous cell carcinoma (OSCC) cell lines and 108 primary OSCC tumors were investigated for activating mutations at exons 9 and 20 as well as amplifications in PIK3CA. PIK3CA missense mutations in exons 9 and 20 were identified in 21.4% (3/14) of OSCC cell lines and 7.4% (8/108) of OSCC tumors by genomic DNA sequencing. An increase in the copy number of PIK3CA, although small, was detected in 57.1% (8/14) of OSCC lines and 16.7% (18/108) of OSCC tumors using quantitative real-time PCR. A significant correlation between somatic mutations of PIK3CA and disease stage was observed: the frequency of mutations was higher in stage IV (16.1%, 5/31) than in a subset of early stages (stages I-III) (3.9%, 3/77; P = 0.042, Fisher's extract test). In contrast, the amplification of PIK3CA was observed at a similar frequency among all stages. AKT was highly phosphorylated in OSCC cell lines with PIK3CA mutations compared to those without mutations, despite the amplification. The results suggest that somatic mutations of the PIK3CA gene are likely to occur late in the development of OSCC, and play a crucial role through the PI3K-AKT signaling pathway in cancer progression.

Adult↗

PubMed2006

Combined hepatocellular carcinoma and cholangiocarcinoma with components of mucinous carcinoma arising in a cirrhotic liver.

A rare autopsy case of combined hepatocellular and cholangiocarcinoma, occurring in a 54-year-old man with liver cirrhosis, is presented. Initial laboratory data included CEA 52.1 ng/mL, DUPAN-2 1600 U/mL, AFP 2 ng/mL, and negativity for hepatitis B surface antigen, hepatitis B early antigen and hepatitis B core antibody. Ultrasonography and CT scan showed a large tumor node in the liver with ringed enhancement, swelling of several para-aortic lymph nodes, and ascites. Clinically, it was not possible to determine whether the hepatic tumor was an intrahepatic cholangiocarcinoma or a metastatic carcinoma. Histologically, the primary lesion was composed solely of hepatocellular carcinoma (HCC) with a trabecular pattern, and the intrahepatic metastases consisted of a variable admixture of HCC and cholangiocarcinoma (CC) with excessive mucin production. Interestingly, the tumor cell cluster showing a trabecular growth pattern produced mucin and had immunohistochemical expression of hepatocyte, cytokeratins 7 and 8. It is concluded that these hepatic tumor cells had both HCC and CC characters.

Adenocarcinoma, Mucinous↗

PubMed2006

HER-2 (c-erbB-2) test update: present status and problems.

HER-2 tests are routinely used for the identification of patients with metastatic breast cancer that is potentially responsive to trastuzumab (herceptin) therapy. Recently, convincing data have been published with regard to the efficacy of trastuzumab as a drug for neoadjuvant therapy or adjuvant therapy for operable primary breast cancer that overexpresses HER-2. It is also noteworthy that a the St. Gallen International Consensus Conference 2005, HER-2 protein overexpression or HER-2 gene amplification has been included as an indicator for higher risk of recurrence for both node-negative and node-positive breast cancers. To measure the HER-2 level, the worldwide consensus appears to be that immunohistochemistry (IHC) should be performed first and, if the results of IHC are uncertain, fluorescence in situ hybridization (FISH) should be performed later, although some investigators argue that FISH should be performed first. These tests should be performed in strict adherence to existing instructions. Quality control is of utmost importance when performing HER-2 tests, both internal and external, for routine diagnosis and in clinical protocol studies.

Breast Neoplasms↗

PubMed2006

Issues in the assessment of the pathologic effect of primary systemic therapy for breast cancer.

BACKGROUND: Emerging evidence suggests that induction of pathologic complete response (pCR) after primary systemic therapy (PST) is, at least to some extent, predictive of survival. However, standards for processing surgical specimens and for histopathologic evaluation of the pathologic response to therapy appear to be lacking. METHODS: To perform a systematic review of representative articles on this topic, a computerized (MEDLINE) search was undertaken followed by a manual search based on the reference lists of the publications identified. RESULTS: Several classification systems have been used to assess pathologic response to PST, the term pCR has not been applied in a consistent standardized manner, and only limited information is available about the reliability and validity of these classification systems. However, definitions of pCR can be summarized as follows: near pCR, only focal invasive tumor residues in the removed breast; quasi pCR, total or near total disappearance of invasive tumor in the removed breast; pCRinv, only in situ tumor residual in the removed breast; comprehensive pCR, no evidence of residual invasive tumor in the removed breast; strict pCR, disappearance of all tumor cells in the removed breast; comprehensive pCR (br+n), no evidence of residual invasive tumor in the breast and axillary nodes; strict pCR (br+n), no malignant tumor cells in the removed breast and axillary nodes. Comparison of the use of the term "pCR" in various trials reveals that it is not applied equivalently in these studies. CONCLUSION: Assessment of pCR needs to be standardized, with verification for reliability and validity. For now, the non-equivalency in the definition of pCR should be taken into account when comparing the results of PST.

Antineoplastic Agents↗

PubMed2006

Clinical significance of immunocytochemistry for PIK3CA as a carcinogenesis-related marker on liquid-based cytology in cervical intraepithelial neoplasia.

The catalytic subunit alpha of phosphatidylinositol 3-kinase (PIK3CA) has been expected to play a role as an important oncogene in uterine cervical carcinoma, whose expression in non-invasive lesions has received considerable attention. We investigated the potential of PIK3CA as a carcinogenesis-related marker for early intraepithelial lesion of the uterine cervix in cytology samples. Seventy-four cases with abnormal cytology suggesting the existence of cervical intraepithelial neoplasia (CIN) lesions, whose findings were histologically confirmed, were selected; they consisted of 20 CIN1, 21 CIN2, and 33 CIN3, respectively. In addition, 17 normal cases, whose cervical cytology revealed no abnormality over three occasions, were selected. Liquid-based cytology specimens were applied for human papillomavirus (HPV) DNA typing and immunocytochemistry using three different antibodies for p16(INK4a), Ki-67 and PIK3CA, respectively. The fraction of immunopositive cells on the slides was calculated and expressed as mean numbers. Receiver operating characteristic (ROC) plots were generated to determine the diagnostic accuracy of each immunocytochemistry test. The mean number of immunopositive cells in the CIN3 group was significantly higher than other groups for all three antibodies. Among all groups, PIK3CA showed a superior specificity to distinguish CIN3 from other groups. Comparison of three markers by ROC curves also revealed that PIK3CA provided the best method for distinguishing CIN3. Thus, expression of PIK3CA was observed in liquid-based cytology in CIN lesions, which suggested its diagnostic significance in addition to the use of routine cervical cancer smear and the HPV screening program.

Biomarkers, Tumor↗

PubMed2006

Gene expression profiles with cDNA microarray reveal RhoGDI as a predictive marker for paclitaxel resistance in ovarian cancers.

In the current study, we identified paclitaxel-resistant related genes by comparing gene expression profiles of paclitaxel-resistant and parent ovarian cancer cell lines. Gene expression profiles of the human ovarian cancer cell line (KF28), cisplatin-resistant cell line (KFr13) induced from KF28, and paclitaxel-resistant cell lines (KF28TX and KFr13TX) induced by exposing KF28 and KFr13 to dose-escalating paclitaxel were compared and analyzed using cDNA microarray. Of 557 human cancer-related cDNA transcripts compared, 5 genes were found to be underexpressed and 5 genes overexpressed in the paclitaxel-resistant KF28TX, while another paclitaxel-resistant KFr13TX had 5 underexpressed and 8 overexpressed genes. Among these genes, overexpression of the ATP-binding cassette subfamily (MDR-1), Rho guanine dinucleotide phosphate dissociation inhibitor beta (RhoGDI) and insulin-like growth factor binding protein 3 (IGFBP-3) was observed in both paclitaxel-resistant cell lines. Using real-time quantitative PCR, we confirmed the array results. We therefore conclude that IGFBP-3, RhoGDI and MDR-1 were correlated with paclitaxel resistance. Moreover, immunohistochemical staining was analyzed in 22 serous ovarian cancer tissues from patients who received paclitaxel-based chemotherapy, and RhoGDI overexpression was observed more frequently in non-responsers than in responders (p=0.004). RhoGDI expression proved to be a predictive marker of paclitaxel resistance not only in paclitaxel-resistant cell lines, but also in clinical samples.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2006

Adjuvant chemotherapy with irinotecan hydrochloride and cisplatin for clear cell carcinoma of the ovary.

Clear cell carcinoma (CCC) of the ovary has distinct characteristics showing resistance to conventional platinum-based regimen. Our aim was to evaluate the effects of combination therapy with irinotecan hydrochloride and cisplatin (CPT-P), comparing to regimen with paclitaxel and platinum (TP). We retrospective reviewed 172 patients with complete surgical staging procedures including lymphadenenctomy. Forty-six patients received CPT-P and 126 patients were treated with TP. Survival of the two groups was compared. Between CPT-P group and TP group, there was no significant difference in median age, performance status, FIGO stage, rate of optimal cytoreduction, and follow-up period. There was no significant difference in progression-free survival of patients with stage I tumors (p=0.95) and suboptimally debulked stage II-IV tumors (p=0.92). Although there was no significant difference of overall survival, progression-free survival of CPT-P group was significantly better than that of TP group in optimally debulked stage II-IV (p=0.03). Multiple regression survival analysis revealed CPT-P regimen (p=0.02) and residual tumor diameter (p<0.01) were both independent prognostic factors in stage II-IV tumors. The combination of CPT-P was shown to have a potential therapeutic benefit for advanced CCC of the ovary, especially for cases with optimal debulking surgery. However, this is a limited retrospective study, therefore we recommend that the CPT-P regimen be evaluated in a larger prospective study.

Adenocarcinoma, Clear Cell↗

PubMed2005

ADAM23, a possible tumor suppressor gene, is frequently silenced in gastric cancers by homozygous deletion or aberrant promoter hypermethylation.

Array-based comparative genomic hybridization (CGH-array) has a powerful potential for high-throughput identification of genetic aberrations in cell genomes. We identified a homozygous loss of ADAM23 (2q33.3) in the course of a program to screen a panel of gastric cancer (GC) cell lines (1/32, 3.1%) for genomic copy-number aberrations using our custom-made CGH-array. Infrequent homozygous deletion of ADAM23 was also seen in primary gastric tumors (1/39, 2.6%). ADAM23 mRNA was expressed in normal stomach tissue, but not in the majority of GC cell lines without homozygous deletion of this gene. Expression of ADAM23 mRNA was restored to gene-silenced GC cells after treatment with 5-aza 2'-deoxycytidine. The methylation status of the ADAM23 CpG island, which showed promoter activity, correlated inversely with its expression. Methylation of this CpG island was observed both in GC cell lines and in primary GC tissues; in primary tumors with a hypermethylated CpG island, expression of ADAM23 was lower than in adjacent noncancerous tissues. Moreover, restoration of ADAM23 in GC cells reduced their numbers in colony-formation assays. These results suggest that genetic or epigenetic silencing by hypermethylation of the ADAM23 CpG-rich promoter region leads to loss of ADAM23 function, which may be a factor in gastric carcinogenesis.

ADAM Proteins↗

PubMed2005

Nuclear expression of cIAP-1, an apoptosis inhibiting protein, predicts lymph node metastasis and poor patient prognosis in head and neck squamous cell carcinomas.

cIAP-1, an apoptosis inhibiting protein, has been suggested to play important roles in the development of cervical and esophageal squamous cell carcinomas (SCCs). In order to clarify the subcellular localization of cIAP-1 and to investigate its clinicopathological significance in head and neck SCCs (HNSCCs), we examined cIAP-1 expression in four oral SCC cell lines by immunocytochemistry and Western blot. Expressions of nuclear and cytoplasmic cIAP-1, caspase-3, and Smac/DIABLO were also examined immunohistochemically in 57 cases of the HNSCCs. cIAP-1 expression was detected in HSC-2, HSC-3, and HSC-4 cells by immunohistochemistry and Western blot. In HSC-2 and HSC-4 cells, cIAP-1 was detected in both the nuclear and cytoplasmic fractions. Nuclear cIAP-1 expression was positive in 17 (30%) of HNSCCs, was correlated with lymph node metastasis (P=0.020) and advanced disease stage (P=0.032), and tended to be correlated with poor patient prognosis (P=0.059). Cytoplasmic cIAP-1 expression showed similar but weaker clinicopathological correlations. Nuclear cIAP-1 expression was inversely correlated with caspase-3 expression, but was correlated with Smac/DIABLO expression. Nuclear cIAP-1 expression appears to be a useful marker for predicting poor patient prognosis in HNSCCs, and may play roles in HNSCCs through the signaling pathway mediated by Smac/DIABLO and caspase-3.

Adult↗

PubMed2005

Usefulness and limitation of multiple endoscopic biopsy sampling for epidermal growth factor receptor and c-erbB-2 testing in patients with gastric adenocarcinoma.

BACKGROUND: Our objective was to examine the utility of endoscopic biopsy specimens in judging the status of epidermal growth factor receptor (EGFR) and c-erbB-2 genes and proteins in the entire tumor. METHODS: Endoscopic biopsy specimens and specimens of whole representative cut surfaces of corresponding surgically resected tumors were obtained from 14 patients with gastric carcinoma, and immunohistochemistry and fluorescence in situ hybridization were then performed to determine the protein expression and gene amplification profiles, respectively, of EGFR and c-erbB-2 in these biopsy and surgical specimens. RESULTS: Among the eight endoscopic biopsy specimens obtained from three gastric carcinomas in which EGFR protein overexpression and gene amplification were judged to be positive in the corresponding surgically resected tissue specimens, EGFR overexpression was detected in three specimens (38%), but EGFR amplification was not detected (0%). Among the 19 endoscopic biopsy specimens obtained from five gastric carcinomas in which c-erbB-2 protein overexpression and gene amplification were judged to be positive in the corresponding surgically resected tissue specimens, c-erbB-2 overexpression and amplification (c-erbB-2/CEP17 ratio) were detected in 14 (74%) and 16 (84%) specimens, respectively. All three cases with EGFR overexpression and all five cases with c-erbB-2 overexpression showed intratumor heterogeneity with regard to their EGFR and c-erbB-2 status, respectively. CONCLUSIONS: The c-erbB-2 status could be adequately assessed not only by examining surgically resected materials, but also by examining multiple endoscopic biopsy specimens. On the other hand, to assess the EGFR status accurately, the use of surgically resected samples appeared to be more reliable than the use of multiple endoscopic biopsy samples.

Adenocarcinoma↗