Matrine improves the hepatic microenvironment and reverses epithelial-mesenchymal transition in hepatocellular carcinoma by inhibiting the Wnt-1/ß-catenin signaling pathway.

OBJECTIVE: Hepatocellular carcinoma (HCC) is a malignant tumor with high morbidity and mortality. Despite rapid progress in targeted therapy and immunotherapy for HCC over the past 10 years, the overall efficacy remains unsatisfactory. This is mainly due to the presence of an intrahepatic microenvironment of cirrhosis in HCC patients, leading to cancer recurrence and drug resistance. METHODS: In this study, we investigated the correlations between the Wnt-1/ß-catenin signaling pathway and the prognosis as well as liver function of HCC patients. Additionally, we conducted in vitro experiments using different concentrations of matrine on HuH-7 cells. Furthermore, we verified the associations between the Wnt-1/ß-catenin signaling pathway, inflammation, and epithelial-mesenchymal transition (EMT) in a rat model of pre-hepatocellular carcinoma. Finally, matrine was employed to treat pre-hepatocellular carcinoma in rats and patients with advanced hepatocellular carcinoma. RESULTS: The results demonstrated the activation of the Wnt-1/ß-catenin signaling pathway, the occurrence of EMT, and exacerbated inflammation in human HCC tissues. In HuH-7 cell experiments, matrine effectively downregulated the Wnt-1/ß-catenin pathway, reversed EMT, and suppressed migration and invasion of HCC cells. In the rat model of pre-hepatocellular carcinoma, matrine dose-dependently inhibited the activation of the Wnt-1/ß-catenin signaling pathway, reversed the occurrence of EMT, and alleviated liver inflammation. Matrine analogues exhibited promising hepatoprotective effects in patients with advanced HCC. CONCLUSIONS: Matrine can reverse EMT, alleviate intrahepatic inflammation, and counteract immune depletion by inhibiting the Wnt-1/ß-catenin signaling pathway in HCC.

Correlation between immune-related adverse events and treatment efficacy of anti-PD1 immunotherapy in patients with esophageal squamous cell carcinoma.

Immune-related adverse events (irAEs) caused by immune checkpoint inhibitors (ICIs) are associated with improved treatment efficacy in certain types of cancer. In the present study, we assessed the association between irAEs and ICI efficacy. Patients with esophageal squamous cell carcinoma (ESCC) who received ICI treatment were stratified into irAEs and non-irAE groups. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were used to evaluate the therapeutic efficacy of ICIs. Of the 78 ICI-treated ESCC patients, 39 developed irAEs. The median OS and PFS for all patients were 600 and 300 days, respectively. Median OS (P<0.001) and PFS (P<0.001) times of the patients with irAEs were longer than those in the non-irAE group. In addition, the DCR of the irAE group was higher than that of the non-irAE group (P=0.006). Univariate analysis indicated that the non-irAE group was associated with a relatively shorter OS [hazard ratio (HR)=3.687, 95% CI, 1.974-6.888, P<0.001] and PFS (HR=2.967, 95% CI, 1.691-5.204, P<0.001). The multifactorial analysis demonstrated that irAE status was an independent predictor of PFS (HR=3.564, 95% CI, 1.786-7.114, P<0.001) and OS (HR=3.288, 95% CI, 1.636-6.606, P=0.001). In conclusion, the present study demonstrated that irAEs could be used to predict improved treatment efficacy in patients with ESCC who received ICI therapy.

Clinical significance of novel identified high-frequency tumor-specific peptides associated signature in predicting disease status of gastric cancer patients.

The effectively early detection and determination of disease progression of gastric cancer (GC) are still required. An emerging demand for identifying the novel targets adherent to cancer cells has been still challenged since those valuable profilings not only could act as for early gastric tumor discovery but also being potential therapeutic views. We have retrospectively analyzed GC biopsies to identify those specific target peptides in association with disease progression. We have detected the polypeptide by liquid mass technology initiated BIO-HIGH innovational assay technology for tumor-specific target peptide identification. We have validated the accessibility and feasibility of multiple target cytotoxic T-lymphocyte for the assessment of potential molecular markers by equally comparing the frequencies of tumor peptides' loci identified in 138 GC patients. The aim was to separate peripheral blood lymphocytes by density gradient centrifugation and use specific target peptides in in vitro culture of lymphocytes. The Cell Counting Kit-8 assay was set up to prove the lymphocytes' proliferation stimulated by identified peptides. Both of GC-specific peptide and shared peptide were detected in the peripheral blood, and the frequencies and quantities were correlated with disease status and cancer differentiation, in which BHGa1510 (78%), BHGa1310 (66%), BHGa0910 (57%), BHGa0310 (54%), BHGa0210 (40%), BHGa0810 (35%), BHGa0110 (33%), and BHGa1410 (30%) were apparently scoped out as high-frequency (HF) peptides could be potentially specific tumor markers. Moreover, BHGa1410 was significantly associated with cancer progression, and BHGa0910 and BHGa0210 were significantly associated with TNM stage. The IHC data have shown that both the HF BHGa1510 and HF BHGa1310 were expressions by 100% in contrast with paracancerous tissues of 40% (p < 0.05) and 33%, respectively (p < 0.05). Those specific peptide pools could be valued in assessment of advanced tumor and differential status in GC patients.

Matrine promotes hepatic oval cells differentiation into hepatocytes and alleviates liver injury by suppression of Notch signalling pathway.

AIMS: Recent studies have shown that the hyperactive Notch pathway is involved in cirrhosis and hepatocellular carcinoma (HCC) development by regulating differentiation of hepatic oval cells (HOCs) into cancer cells. The aim of this study was to investigate whether matrine can alleviate liver injury and promote HOC differentiation into hepatocytes by suppression of Notch pathway. MAIN METHODS: We evaluated the expression of Notch-1, Jagged-1, and Hes-1 in HCC tissue by immunohistochemistry. Stem cell characteristics of HOCs were evaluated by CCK-8, cell cycle, and apoptosis. The expression of Notch pathway, HOC markers and albumin (ALB) was detected by immunohistochemistry, QRT-PCR and western blotting. The effects of matrine in protecting liver in vivo were investigated in a rat Solt-Farber precancerous model. KEY FINDINGS: We found an abnormal activated Notch pathway in HCC tissue, and the hyperactive Notch pathway was strongly associated with poor liver function in patients with cirrhosis with HCC. Using siNotch-1 to inhibit Notch pathway confirmed that Notch pathway could maintain stem cell characteristics of HOCs. Matrine inhibited stem cell characteristics of HOCs, the expression of Notch pathway and HOC markers but upregulated ALB. Matrine in combined with siNotch-1 RNA decreased the more potently inhibited HOC markers and Notch pathway. In rat Solt-Farber precancerous model, prophylactic application of matrine alleviated liver injury, downregulated Notch pathway and HOC markers, and upregulated ALB in a dose-dependent manner. SIGNIFICANCE: Matrine could promote the differentiation of HOCs into hepatocytes by inhibiting the Notch signalling pathway and alleviate liver injury.

Matrine prevents the early development of hepatocellular carcinoma like lesions in rat liver.

Matrine (C15H24N2O) is an alkaloid extracted from the Chinese herb Sophora flavescens that has anti-fibrotic and anti-cancer properties. The aim of the present study was to determine the chemopreventive effect of matrine on the development of primary hepatocellular carcinoma (HCC) and its possible association with the suppression of the Notch signaling pathway. The rats were randomly divided into four groups: Control, model, low-dose matrine and high-dose matrine groups. The model was established by combining a partial hepatectomy with diethylnitrosamine (DEN) + 2-acetylaminofluorene (2-AAF). Low- and high-dose matrine groups received intragastric administration of matrine (0.25 and 2.5 g/l of matrine, respectively). DEN + 2-AAF injections and hepatectomy were not performed in the control group. All rats were sacrificed 2, 4 and 7 weeks after hepatectomy. HCC-like histopathological lesions were detected using hematoxylin and eosin staining. The expression levels of α-1-fetoprotein (AFP), albumin (ALB), Notch1 and Hes1 were analyzed using immunohistochemistry. Hepatic lobule structure loss, liver tissue necrosis and inflammatory cell infiltration, and edema degeneration were observed in the model group. By contrast, hepatocyte cord structure was restored and hepatocyte edema degeneration was significantly reduced after 7 weeks of treatment with matrine. In addition, compared with the model group, matrine reduced the expression of AFP, increased the expression of ALB and reduced the expression of Notch1 and Hes1 (only for high-dose matrine; all P<0.05). The findings suggested that matrine could prevent the early development of HCC-like lesions in a rat model, possibly by modulating Notch pathway activation.

Clinical efficacy and safety of paclitaxel liposomes as first-line chemotherapy in advanced gastric cancer.

Aim: To compare the performance of first-line paclitaxel liposome + oxaliplatin and SOX (tegafur/gimeracil/oteracil + oxaliplatin) in advanced gastric cancer patients. Materials & methods: Stage IIb-IV gastric cancer patients underwent either first-line paclitaxel liposome + oxaliplatin (n = 52) or SOX (n = 69) between 2010-2013, and followed up until 2015 or death. Results: Both groups had similar objective response rate (p = 0.48) and disease control rate (p = 0.992) after two chemotherapy cycles, median progression-free survival (p = 0.495) and median overall survival (p = 0.208). Liposome group had significantly lower rate of grade I-II platelet decline and liver function damage (p = 0.04 and 0.019). Multivariate COX regression identified pre-treatment neutrophil-to-lymphocyte ratio as an independent prognostic factor. Conclusion: First-line paclitaxel liposome + oxaliplatin has comparable efficacy, but causes reduced adverse reactions in advanced gastric cancer as compared with SOX.

Methicillin-resistant staphylococcus aureus isolates in a hospital of shanghai.

Methicillin-resistant Staphylococcus aureus (MRSA) strains are now common both in the health care setting and in the community. Active surveillance is critical for MRSA control and prevention. Specimens of patients (200 patients with 1119 specimens) as well as medical staff and hospital setting (1000 specimens) were randomly sampled in a level 2 hospital in Shanghai from September 2011 to August 2012. Isolation, cultivation and identification of S. aureus were performed. Totally, 67 S. aureus strains were isolated. 32 S. aureus strains were isolated from patient samples; 13 (13/32, 40.6%) of the 32 S. aureus isolates were MRSA; sputum sample and patients in the department of general internal medicine were the most frequent specimen and patient group for S. aureus strains isolation. Remaining 35 S. aureus strains were isolated from the medical staff and hospital setting; 20 (20/35, 57.1%) of the 35 S. aureus isolates were MRSA; specimens sampled from doctors and nurses' hands and nose and hospital facilities were the most frequent samples to isolate S. aureus. Resistant and virulent genes detection showed that, all 33 MRSA strains were mecA positive which accounts for 49.3% of the 67 S. aureus strains; 38 isolates were Panton-Valentine leukocidin (PVL) gene positive which accounts for 56.7% of the 67 S. aureus strains; and 17 (17/67, 25.4%) isolates are mecA and PVL genes dual positive. Multidrug-resistant strains of MRSA and PVL positive S. aureus are common in patients, medical staff and hospital setting, the potential health threat is worthy of our attention.

Acute gastroenteritis outbreak caused by a GII.6 norovirus.

AIM: To report an acute gastroenteritis outbreak caused by a genogroup 2 genotype 6 (GII.6) strain norovirus in Shanghai, China. METHODS: Noroviruses are responsible for approximately half of all reported gastroenteritis outbreaks in many countries. Genogroup 2 genotype 4 strains are the most prevalent. Rare outbreaks caused by GII.6 strains have been reported. An acute gastroenteritis outbreak occurred in an elementary school in Shanghai in December of 2013. Field and molecular epidemiologic investigations were conducted. RESULTS: The outbreak was limited to one class in an elementary school located in southwest Shanghai. The age of the students ranged from 9 to 10 years. The first case emerged on December 10, 2013, and the last case emerged on December 14, 2013. The cases peaked on December 11, 2013, with 21 new cases. Of 45 students in the class, 32 were affected. The main symptom was gastroenteritis, and 15.6% (5/32) of the cases exhibited a fever. A field epidemiologic investigation showed the pathogen may have been transmitted to the elementary school from employees in a delicatessen via the first case student, who had eaten food from the delicatessen one day before the gastroenteritis episodes began. A molecular epidemiologic investigation identified the cause of the gastroenteritis as norovirus strain GII.6; the viral sequence of the student cases showed 100% homology with that of the shop employees. Genetic relatedness analyses showed that the new viral strain is closely related to previously reported GII.6 sequences, especially to a strain reported in Japan. CONCLUSION: This is the first report to show that norovirus strain GII.6 can cause a gastroenteritis outbreak. Thus, the prevalence of GII.6 noroviruses requires attention.

PFOS and PCB 153 have direct adverse effects on neonatal testis modeled using a coculture of primary gonocyte and sertoli cells.

Perfluorooctane sulfonate (PFOS) is widely used in industry; it is nonbiodegradable and persistent in the human body and in the environment. Although reports have indicated that young people might have higher PFOS levels in serum or blood than do older people, its adverse effects on neonatal testicular cells had not been investigated previously. PCB 153 is one of the most prevalent polychlorinated biphenyl (PCB) congeners in biological tissues, but the direct adverse effect of PCB 153 on neonatal testis remains unclear. In this study, we exposed a neonatal Sertoli cell/gonocyte coculture system to PFOS and PCB 153 individually at concentrations of 0, 1, 10, 50, and 100 µM for 24 h. Exposure to either compound reduced the cell viability and induced the production of reactive oxygen species (ROS) in dose-dependent manners, with PCB 153 having a greater effect than PFOS. Whereas PCB 153 induced apoptosis significantly from 10 µM, PFOS induced no obvious change. Morphologically, both PCB 153 and PFOS induced changes in the vimentin and actin filaments in the Sertoli cells, as investigated using confocal argon ion laser scanning microscopy; here, PFOS exhibited a more dramatic effect than did PCB 153. Furthermore, doses of 50 µM for PFOS and 10 µM for PCB 153 were the key concentrations that produced significant differences between the control and exposure groups. We suggest that both PCB 153 and PFOS directly affect neonatal gonocyte and Sertoli cells; the production of ROS and the change in the cytoskeleton in Sertoli cells might be causes.

Neonatal exposure to benzo[a]pyrene decreases the levels of serum testosterone and histone H3K14 acetylation of the StAR promoter in the testes of SD rats.

Although benzo[a]pyrene (BaP) is an environmental endocrine disrupter, it has been unclear whether neonatal exposure to BaP affects the testosterone level and, if so, whether this influence persists into adulthood. In this present study, we gave neonatal rats (through oral gavages) doses of 0, 5, 10, or 25mg/kg day of BaP in corn oil from postnatal day 1 (PND 1) to PND 7. The rats were sacrificed at PND 8, PND 35, and PND 90. BaP exposure was confirmed through the induction of liver and testis CYP1A1 mRNA expression at PND 8 (i.e., immediately after exposure). The testicular daily sperm production and the sperm counts of the epididymis cauda at PND 90 were significantly lower than those of the control. The serum testosterone levels decreased markedly at PND 8, PND 35, and PND 90 after neonatal BaP exposure relative to those of the control. The mRNA expressions of StAR also decreased relative to those of the control at PND 8, PND 35, and PND 90, although the mRNA expressions of P450c17 and 17ß-HSD were suppressed significantly only at PND 8. To further elucidate the mechanism of the persistent decrease in the mRNA expression of StAR, we determined the histone acetylation level in the StAR promoter. The extent of acetylation of H3K14 in the determined region decreased after neonatal exposure to BaP; this phenomenon persisted to the adult stage. Our results indicate that neonatal exposure to BaP damages testosterone production and sperm counts in the long term, possibly as a result of epigenetic regulation in the StAR promoter region.

Mesenteric involvement in giant cell arteritis. An underrecognized complication? Analysis of a case series with clinicoanatomic correlation.

We reviewed the clinical manifestations of mesenteric vasculitis due to giant cell arteritis (GCA) and considered features of the mesenteric anatomy in relationship to disease expression. We compiled and reviewed a case series by systematic identification of patients previously reported in the English-language literature to have mesenteric involvement from known GCA. Included in the analysis was a detailed case review of a patient with GCA and small bowel infarction seen at our institution. Twelve patients were identified with mesenteric ischemia attributed to GCA. Concomitant cranial and abdominal symptoms were present in 7 of the 12 patients, and cranial symptoms were absent in 5 patients who presented with abdominal complaints. The abdominal symptoms fell within a spectrum ranging from chronic postprandial symptoms to acute abdominal pain. Survival was observed in only 6 of the 12 cases, 3 of whom required bowel resection and were treated with high-dose corticosteroids. Review of the anatomic features of the specialized splanchnic circulation reveals an extensive collateral network that may protect against early disease expression from ischemia, despite mesenteric arteritic involvement. Mesenteric vasculitis resulting in small bowel infarction has only rarely been described in GCA but represents a serious and potentially treatable complication. We propose an explanation, based on mesenteric vascular anatomy, for the infrequency of symptomatic expression of this entity and suggest that occult mesenteric GCA may be present far more often than recognized.

Expression of a novel oncofetal mRNA-binding protein IMP3 in endometrial carcinomas: diagnostic significance and clinicopathologic correlations.

Insulin-like growth factor-II mRNA-binding protein 3 (IMP3) is a newly identified oncofetal mRNA-binding protein that is involved in embryogenesis and carcinogenesis of some malignant neoplasms. To investigate the diagnostic and clinicopathologic significance of this protein in endometrial carcinomas, we evaluated immunohistochemical expression of IMP3 in the two most common forms of endometrial malignancies, endometrioid adenocarcinoma and serous carcinoma. We selected 167 endometrial adenocarcinoma cases including 122 cases of endometrioid adenocarcinoma and 45 cases of serous carcinoma. Twenty samples of benign endometrium obtained from 20 patients with nonmalignant uterine lesions were used as controls. Positive immunohistochemical stain for IMP3 was identified in all serous carcinoma cases, among which, 39 (86%) and 3 (7%) cases showed IMP3 immunoreactivity in >50%, and 21-50, or 6-20% of tumor cells, respectively. Immunohistochemical reaction intensity for IMP3 was identified to be strong in 38 (84%) and intermediate in 7 (16%) cases of serous carcinoma. Fifty-four (44%) cases of endometrioid adenocarcinoma were negative for IMP3. Thirty (25%), 20 (16%), 10 (8%), and 8 (7%) cases of endometrioid adenocarcinoma demonstrated positive immunoreactivity for IMP3 in 1-5, 6-20, 21-50, and >50% of the tumor cells. Strong IMP3-staining intensity was noted in 34 (28%), intermediate in 26 (21%), and weak in 8 (7%) cases of endometrioid adenocarcinoma. All 20 control cases were negative for IMP3. To compare p53 with IMP3 expressions, we found that 35 (78%) of the serous carcinoma cases showed strong p53 immunohistochemical activity in >50% of the tumor cell nuclei. In contrast, 11 of 112 (10%) endometrioid adenocarcinoma cases demonstrated strong p53 positivity in >50% of the tumor cell nuclei. In conclusion, our findings demonstrate significant expression of IMP3 in serous carcinoma as compared to endometrioid adenocarcinoma (P<0.0001). Expression of IMP3 and p53 may be helpful biomarkers in the distinction of endometrial serous carcinoma from endometrioid adenocarcinoma. In addition, expression of IMP3 in endometrioid adenocarcinoma correlates with higher nuclear and architecture grades of the tumor (P=0.0000 and P=0.0002, respectively).

IMP3 is a novel biomarker for adenocarcinoma in situ of the uterine cervix: an immunohistochemical study in comparison with p16(INK4a) expression.

Adenocarcinoma in situ of the uterine cervix remains a diagnostic challenge in a small proportion of cases. This suggests a need for biomarker that may be of help in establishing the diagnosis. The aim of this study was to evaluate the potential of insulin-like growth factor-II mRNA-binding protein 3 and cyclin-dependent kinase inhibitor p16(INK4a) as biomarkers for adenocarcinoma in situ. Forty-four samples of adenocarcinoma in situ from 40 patients and 23 control cases of benign uterine cervix were included in this study. In addition to benign endocervical epithelium, 19 of these 23 control cases also showed focal tubal metaplasia. Cytoplasmic immunoreactivity for insulin-like growth factor-II mRNA-binding protein 3 was identified in 41 (93%) adenocarcinoma in situ samples, among which, 29 (71%), 10 (24%), and 2 (5%) samples showed insulin-like growth factor-II mRNA-binding protein 3 positive staining in 50% or more, >5 to <50 and <5% of adenocarcinoma in situ lesional cells, respectively. Immunohistochemical reaction intensity for insulin-like growth factor-II mRNA-binding protein 3 was found to be strong in 34 adenocarcinoma in situ samples, intermediate in five, and weak in two. All 23 control cases were negative for insulin-like growth factor-II mRNA-binding protein 3. p16(INK4a) expression was identified in all of the adenocarcinoma in situ samples with intermediate staining intensity seen in seven samples and strong in the remainder. Fourteen of 19 (74%) tubal metaplasia cases showed p16(INK4a) immunoreactivity in >50% of the tubal metaplastic epithelium with staining intensity ranging from weak to strong. Our findings demonstrate significant expression of insulin-like growth factor-II mRNA-binding protein 3 and p16(INK4a) in adenocarcinoma in situ as compared to benign endocervical glands, suggesting that expression of these biomarkers may be helpful in the distinction of adenocarcinoma in situ from benign endocervical glands, particularly in difficult borderline cases.

Analysis of RNA-binding protein IMP3 to predict metastasis and prognosis of renal-cell carcinoma: a retrospective study.

BACKGROUND: Distant metastasis is the main cause of death from renal-cell carcinoma, and the metastatic potential of tumours is often unpredictable. We aimed to investigate whether IMP3, an oncofetal RNA-binding protein, can be used as a biomarker to predict metastasis and prognosis of renal-cell carcinoma. METHODS: We studied 501 primary and metastatic renal-cell tumours. 371 patients with localised primary tumours were further investigated by use of survival analysis. We assessed IMP3 expression in tumour tissues by immunohistochemistry, and IMP3 mRNA and protein expression in selected tissues by quantitative real-time PCR and western blot analysis. FINDINGS: Compared with non-metastatic renal-cell tumours, IMP3 expression was greatly increased not only in metastatic tumours but also in a subset of primary tumours that were likely to subsequently develop metastases. Patients with primary localised tumours that did not express IMP3 had a longer metastasis-free survival and overall survival than did those with tumours expressing IMP3 (p<0.0001). Patients with IMP3-positive localised tumours had a much lower 5-year metastasis-free survival than did those with IMP3-negative tumours (for stage I tumours, 44% vs 98%, hazard ratio 17.18 [95% CI 7.82-37.78]; stage II, 41% vs 94%, 10.14 [3.46-29.68]; stage III, 16% vs 62%, 4.04 [2.23-7.31]). IMP3 expression was also associated with reduced 5-year overall survival (stage I, 32% vs 89%, 6.44 [3.63-11.42]; stage II, 41% vs 88%, 6.93 [2.63-18.27]; stage III, 14% vs 58%, 3.46 [1.98-6.05]). Multivariable analysis of IMP3 status (positive vs negative) in primary tumours showed hazard ratios of 5.84 (95% CI 3.60-9.49) for metastasis-free survival and 4.01 (2.66-6.05) for overall survival (both p<0.0001), which were much higher than hazard ratios associated with other independent risk factors. INTERPRETATION: IMP3 is an independent prognostic marker that can be used at initial diagnosis of renal-cell carcinoma to identify patients who have a high potential to develop metastasis and who might benefit from early systemic treatment.

Renal cell carcinoma presenting as a perineal mass: case report and review of the literature.

Perineal involvement in renal cell carcinoma (RCC) has not been reported. Vaginal metastases of RCC are also rare. We present a case of metastatic RCC, initially presenting as a perineal cyst. A 53-year-old woman presented with a perineal cyst, which was excised and diagnosed as clear cell carcinoma. A workup further revealed a vaginal mass and a renal tumor. A nephrectomy and local vaginal excision were performed, leading to the diagnosis of metastatic RCC. This case illustrates the variability in RCC presentation. Also, because vaginal clear cell carcinoma is rare, all such lesions should be considered potentially renal in origin.

Primary angiosarcoma of the ovary: a case report of Stage I disease.

BACKGROUND: There are 20 documented cases of primary ovarian angiosarcoma. Most patients present with metastatic disease and respond poorly to chemotherapy. There is little information available to counsel early-staged patients on the need for or efficacy of adjuvant chemotherapy. CASE: We present a case of Stage Ic primary ovarian angiosarcoma treated with 3 cycles of adjuvant MAID chemotherapy. The patient is without evidence of disease 10 months post-operatively. CONCLUSION: A review of the literature indicates a potential role for MAID chemotherapy in the treatment of ovarian angiosarcomas. Detection of Stage I disease appears to confer a better prognosis regardless of the utilization of adjuvant chemotherapy.

Using an AMACR (P504S)/34betaE12/p63 cocktail for the detection of small focal prostate carcinoma in needle biopsy specimens.

We assessed the usefulness of immunohistochemical analysis with a 3-antibody cocktail (alpha-methylacyl coenzyme A racemase [AMACR, or P504S], 34betaE12, p63) and a double-chromogen reaction for detection of limited prostate cancer in 138 needle biopsy specimens, including 82 with small foci of prostatic adenocarcinoma and 56 benign prostates. When carcinoma was present, red cytoplasmic granular staining (AMACR) in the malignant glands and cells and dark brown nuclear (p63) and cytoplasmic (34betaE12) staining in basal cells of adjacent nonmalignant glands were found. Of 82 cases of small foci of prostatic adenocarcinoma, 78 (95%) expressed AMACR; all malignant glands were negative for basal cell staining. All benign glands adjacent to malignant glands were recognized easily by basal cell marker positivity and little or no AMACR expression. No benign glands were simultaneously positive for AMACR and negative for basal cell markers (specificity, 100%). There were no differences in intensity and numbers of positive glands with double-chromogen staining compared with using 1-color staining. Our results indicate that immunohistochemistry with a 3-antibody cocktail and double chromogen is a simple and easy assay that can be used as a routine test, which overcomes the problems of studying small lesions in prostate needle biopsies with multiple immunohistochemical stains.