Positive P53 Staining Research Articles

Comparison of thymidine phosphorylase expression and prognostic factors in gallbladder and bile duct cancer

BackgroundBiliary tract cancers have limitations in information about different location-related pathogenesis and clinico-pathological characteristics. The goal of this study was to investigate anatomical site-related similarities and differences in biliary tract cancers and to assess the expression and clinical significance of functional proteins such as p53, cyclin D1, survivin, thymidine phosphorylase, and ERCC1.MethodsOne hundred and sixty-one patients with biliary tract adenocarcinomas, who underwent curative or palliative surgery in a single institution between October 1994 and December 2003 were evaluated, retrospectively. The level of protein expression of p53, cyclin D1, survivin, thymidine phosphorylase, and ERCC1 was assessed by immunohistochemistry.ResultsWith respect to clinico-pathological characteristics, gallbladder cancer was more frequent in women, and bile duct cancer was more common in men. Perineural invasion was more common in bile duct cancer. Recurrence as a distant metastasis was more common in gallbladder cancer. Immunohistochemical analysis revealed that thymidine phosphorylase expression was significantly higher in gallbladder cancer than in bile duct cancer. Positive thymidine phosphorylase and p53 staining were associated with an advanced stage. Differentiation, vascular invasion, perineural invasion, lymphatic invasion, lymph node metastasis, and TNM stage independently predicted poor prognosis in biliary tract cancer. These correlations were seen more clearly in gallbladder cancer. The immunohistochemical staining patterns of p53, cyclin D1, survivin, thymidine phosphorylase, and ERCC1 showed no prognostic significance in biliary tract cancers.ConclusionsWe concluded that gallbladder and bile duct cancers are considered to be separate diseases with different clinico-pathological characteristics and prognostic factors. In addition, we hypothesize that high expression of thymidine phosphorylase by gallbladder cancer results in a higher response rate to capecitabine by gallbladder cancer than bile duct cancer.

Single-center experience of male breast cancer: Molecular pathology and potential treatment implications.

e21118 Background: Male breast cancer (MBC) is an uncommon disease. In contrast to female breast cancer, information regarding molecular pathology and treatment is limited. The aim of this study was to examine the molecular pathology and receptor biology in Irish men with breast cancer. Methods: Ten patients with MBC were identified from 1997-2008 from a single Irish hospital and the expression of the molecular markers were determined by immunochemistry. We examined the expression of oestrogen receptors (ER), progesterone receptors (PgR), HER-2/neu (EGFR 2), EGFR 1 and p53 mutation. Results: The majority of patients (8/10) were of ductal histologic type and similarly the majority were high grade (grade III - 7/10). All 10 patients had positivity of ER in tumours and in 9 of these 10, PgR was positive. No patients had (EGFR 2) HER-2 over-expression by immunochemistry or gene amplification. All 10 patients had negative staining for EGFR 1. Greater than 30% of tumour cells showed positive staining for p53, and thus by our criteria 6/10 patients were positive for p53 expression. Conclusions: Oestrogen receptor positivity was present in all our patients and this in keeping with the international literature which shows significantly higher ER positivity in male by comparison with female breast cancer. Both high levels of ER positivity and grade III tumours occurred in Irish MBC, in contrast to female patients where there is an inverse relationship between these pathological features. Since its first use in MBC tamoxifen remains the most potent endocrine therapy for male breast cancer. New molecular targeting agents (eg., histone deacetylase [HDAC]) inhibitors could have particular benefits in enhancing tamoxifen efficiency in MBC in view of the high levels of ER expression. Also dose escalation of tamoxifen supported by recent pharmacogenetics studies may be relevant to this group of patients. In view of > 50% of patients showing abnormal p53 assessments, alternative therapeutic strategies for this subgroup, such as proteasomal inhibitors could be explored. No significant financial relationships to disclose.

Metastatic Carcinomas in the Cervix Mimicking Primary Cervical Adenocarcinoma and Adenocarcinoma In Situ

Metastatic tumors within the cervix are uncommon if one excludes endometrial carcinoma, which involves the cervix by direct spread. A variety of other neoplasms rarely metastasize to the cervix and, in most cases, the diagnosis is straightforward because of a combination of clinical and pathologic parameters, common features of metastatic carcinoma within the cervix including predominant involvement of the deep stroma, absence of surface involvement and of an in situ component, and prominent lymphovascular permeation. We describe 6 cases of metastatic adenocarcinoma involving the cervix with superficial "mucosal" involvement mimicking primary cervical adenocarcinoma or adenocarcinoma in situ. In 5 cases, the primary adenocarcinoma was in the ovary or peritoneum and was of serous (4 cases) or clear-cell (1 case) type. In the other case, the primary neoplasm was in the pancreas and this was initially interpreted as a primary cervical adenocarcinoma. In the cases of primary ovarian or peritoneal carcinoma, the mucosal tumor within the cervix, which was discovered at the same time as the ovarian or peritoneal neoplasm, raised the possibility of synchronous independent lesions or metastasis from the cervix to the ovary or peritoneum. Positive staining for WT1, p53, and estrogen receptor in the cases of serous carcinoma and an absence of human papillomavirus by linear array genotyping in all cases was of value in excluding a primary cervical neoplasm, although these ancillary studies are supplementary to microscopic examination. In those cases with an ovarian or peritoneal primary, the likely pathogenesis of the cervical involvement is transtubal and intrauterine spread. It is important for the pathologist to be aware of the possibility of cervical mucosal metastasis to avoid an erroneous diagnosis of a primary cervical adenocarcinoma or adenocarcinoma in situ.

Abstract 3237: Establishment of a new invasive urinary bladder cancer model using human c-Ha-ras proto-oncogene transgenic rats

Abstract To establish animal models for identifying mechanisms of urinary bladder cancer (UBC) invasion, male human c-Ha-ras proto-oncogene transgenic rats (Hras 128) were divided into 5 groups and treated with 0.05% N-butyl-N-(hydroxybutyl)nitrosameine (BBN) in drinking water and/or 0.1% phenylethyl isothiocyanate (PEITC) in diet, respectively, as follows: BBN (8 wks)→PEITC (8 wks); PEITC (8 wks)→BBN (8 wks); PEITC alone (16 wks); BBN alone (16 wks); non-treatment. At the end of week 16, incidences of invasive UBC in BBN→PEITC and BBN alone groups were 77% (10/13 rats) and 56% (5/9 rats), respectively. The average number of invasive UBC in BBN→PEITC and BBN alone groups were 1.3 ± 0.9 and 0.7 ± 0.7/rat, respectively. Both incidence and numbers of invasive UBC tended to be higher in BBN→PEITC group compared to the BBN alone group. Furthermore, non-invasive UBC were also found in all rats of above 2 groups. No tumors were found in other groups. p53 positive staining were observed in 58% of invasive UBC and 9% of non-invasive UBC in BBN→PEITC group that is similar to positive incidences in human UBCs. These findings indicated that treatment of Hras 128 rats with BBN followed by PEITC induced high incidences of both non-invasive and invasive UBC, and therefore provide a useful comparison model for explore the mechanisms of UBC invasion. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3237.

Abstract 803: Expression of poly(adenosine diphosphate-ribose) polymerase (PARP) and p53 in epithelial ovarian cancer

Abstract Objectives: PARP, poly(adenosine diphosphate-ribose) polymerase, is a damage sensing protein that is essential to the repair of DNA single-strand breaks. P53 acts as a “genome guardian” molecule that in response to DNA damage mediates cell cycle arrest or induces apoptosis. PARP and p53 function synergistically in repairing DNA damage and suppressing chromosomal rearrangements. The aim of this study was to determine the expression of PARP and p53 in epithelial ovarian cancer (EOC) and correlate with clinico-pathologic characteristics. Methods: PARP and p53 was examined using immuno-histochemistry applied on a tissue microarray of 189 EOC. PARP and p53 expression were examined in relation to clinco-pathologic variables, including age of diagnosis, stage, grade, histologic type, optimal debulking, progression free survival and overall survival. Progression free survival and overall survival were estimated by Kaplan-Meier method, and statistical significance was calculated by the log-rank test. Results: PARP expression was demonstrated in 61% (115/189) of specimens and 99/185 (54%) samples exhibited p53 staining. PARP positive tumors tended to have higher grade (P = 0.03) and complete response to initial treatment (P = 0.009). Patients with positive p53 staining tended to have higher stage of disease (P = 0.004) and there was a trend of patients with positive p53 and weak PARP expression to increase the likelihood of disease progression (OR 2.25 (CI 0.389-13)). The median follow-up was 40 months. However, there were no significant associations between PARP and p53 expression. There was no significant difference in disease free or overall survival for PARP or p53. Conclusion: This study indicates that PARP and p53 are upregulated in EOC with higher grade tumors and more advanced stages, respectively, and may serve as a marker of aggressive disease behavior. Additional studies are warranted to evaluate the role of PARP and p53 expression as a predictor of response to initial treatment, and to identify patients that may benefit from alternative treatments in the adjuvant setting. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 803.

Ancillary testing in liquid based cytology to distinguish cervical glandular neoplasia from tuboendometrial metaplasia in a young woman

A 33-year old woman had a cervical sample taken at colposcopy clinic. Seven years prior to this, at the age of 26, she had had a cytological diagnosis of cervical glandular neoplasia (cytology descriptor indicated cells suspicious of endocervical neoplasia) and severe dyskaryosis. Confirmation and treatment were by LLETZ and knife cone, and, in keeping with England and Wales National Health Service guidelines, this woman was under follow-up by the colposcopy clinic. Intervening cytological follow-up included a number of negative cytological samples interspaced with one equivocal report. A recent repeat cytology which was rather cellular contained several hyperchromatic crowded cell groups (HCCG's). Careful examination revealed benign endometrial clusters, LUS, TEM and endocervical cells in strips showing pseudostratification and loss of polarity. Following an agar block, there was positive staining for p16 and Ki-67 in the abnormal groups whilst the benign TEM cells stained positive for bcl-2.

P16INK4A and MIB-1: An immunohistochemical expression in preneoplasia and neoplasia of the cervix

To evaluate the potential of p16INK4A and MIB-1 and to compare the expression and interrelationship of these markers in cervical preneoplasias and neoplasias. Immunohistochemical analysis of p16 and MIB-1 was performed in n = 63 tissue sections and by matching the corresponding Papanicolaou smears. Staining intensity for p16 was determined using the 0-3 grading system. For MIB-1, labelling indices (LI) were calculated and grading was performed using the I-III scoring system. No positive staining of p16 was observed in the normal cervical epithelium. With increasing severity of cervical intraepithelial neoplasias (CIN), the p16 expression increased progressively. Significant up-regulation of p16 was observed in carcinoma cervix. MIB-1 LI was observed to increase with increasing grades of CIN, and significant overexpression of MIB-1 was observed in carcinoma cervix. Correlation between grades of p16 and that of MIB-1 among cervical neoplasias showed an increasing p16 expression with consistently increasing MIB-1 LI in the groups of increasing severity. This pattern of overexpression of p16 and MIB-1 demonstrate their use as a diagnostic marker for cervical neoplastic lesion. Therefore, p16 and MIB-1 markers in tissue sections can be used as an adjunct to definitively diagnose preneoplastic and neoplastic lesions in the cervix.

A rare case of isolated duodenal metastases from hepatocellular carcinoma associated with p53 and ki-67 expression: a case report

Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver worldwide. The incidence of HCC is increasing in North America secondary to rises in chronic liver disease from alcohol abuse and viral hepatitis. HCC most commonly metastasizes hematogenously or through lymphatics to the lungs and regional lymph nodes. Involvement of small bowel is rare and typically results from direct invasion and extension. We examined the molecular features related to this extremely rare case of isolated duodenal metastasis of HCC and noted p53 and Ki-67 positive staining. Here, we review the possible molecular and immunohistochemical studies that may aid definitive diagnosis and the evidence for the management of metastatic hepatocellular carcinoma.

P53 Genotype Predicts Response to Chemotherapy in Patients with Squamous Cell Carcinoma of the Esophagus

Response to chemotherapy and anatomical spread are significant prognostic factors in patients with esophageal squamous cell carcinoma (ESCC) treated by chemotherapy then surgery. Predicting the response to chemotherapy would allow significant optimization of cancer treatment. Genomic mutation and protein expression of p53 were investigated retrospectively by polymerase chain reaction (PCR) single-strand conformation polymorphism (SSCP) and immunohistochemistry (IHC) using biopsy specimens from 77 ESCC patients before chemotherapy with 5-fluorouracil, adriamycin, and cisplatin. p53 status was correlated with various clinicopathological factors. Thereafter, we performed a prospective study of 20 consecutive patients to test our prediction model. The retrospective study showed mutant p53 genotype and positive p53 IHC staining in 46.8 and 55.8% of patients, respectively, which was not associated with patient's clinicopathological findings including initial tumor stage. Objective response to chemotherapy was observed in 65.9% of patients with wild genotype, but in only 16.7% of patients with mutant genotype. Patients with mutations in p53 therefore showed significantly poorer prognosis than those without mutant p53. In contrast, p53 IHC staining did not correlate with response to chemotherapy, curative resection rate or prognosis. In the prospective study, p53 mutation was seen in 50% (10/20) of patients and was again consistently associated with poorer response to chemotherapy and poorer prognosis. p53 genotype of pretreatment biopsy is a potentially useful predictor of response to chemotherapy and prognosis in ESCC patients. This information might be valuable to clinicians in deciding on the optimal clinical strategy in patients with ESCC.

The p53-p21(waf1) pathway and centrosome amplification in oral squamous cell carcinomas

To elucidate the possible role of p53-p21(waf1) pathway for centrosome amplification in oral squamous cell carcinoma (OSCC). Formalin-fixed, paraffin-embedded tissues of 8 cases of normal oral epithelium tissues and 27 cases of OSCC tissues were examined for the expression of p21(waf1) and mutated p53 proteins by flow cytometry and immunohistochemistry, and centrosome status was investigated by indirect immunofluorescence double staining with antibodies to centrosome protein gamma-tubulin and cytokeratin. The correlation between p21(waf1), p53 and centrosome amplification in OSCC was statistically analyzed by SPSS 12.0. All normal oral epithelium tissues showed normal centrosomes (1-2 centrosomes per cell)in epithelium cells, while 21 out of 27 cases (78%) of OSCC showed the evidence of centrosome amplification characterized by supernumerary centrosomes ( >2 centrosomes per cell) in a fraction of tumor cells. The quantity of p21(waf1) protein was lower in OSCC with centrosome amplification [(0.878 +/- 0.081)] than that in OSCC without centrosome amplification [(0.952 +/- 0.018), t = 3.838, P < 0.01], and negative correlations were found between the quantity of p21(waf1) protein and the degree of centrosome amplification (r = -0.472, P < 0.05), as well as the positive staining of p53 (r = -0.491, P < 0.01). p53-p21(waf1) pathway might involve in centrosome duplication cycle in OSCC. Down-regulated p21(waf1) protein, via p53 transactivation-dependent mechanism, was likely a contributing factor towards centrosome amplification in OSCC.

High Incidence of Protein-Truncating TP53 Mutations in BRCA1-Related Breast Cancer

Approximately half of all hereditary breast cancers are compromised in their DNA repair mechanisms due to loss of BRCA1 or BRCA2 function. Previous research has found a strong correlation between BRCA mutation and TP53 mutation. However, TP53 mutation status is often indirectly assessed by immunohistochemical staining of accumulated p53 protein. We sequenced TP53 exons 2 to 9 in 21 BRCA1-related breast cancers and 37 sporadic breast tumors. Strikingly, all BRCA1-related breast tumors contained TP53 mutations, whereas only half of these tumors stained positive for p53 accumulation. Positive p53 staining correlates with the presence of TP53 hotspot mutations in both BRCA1-related and sporadic breast tumors. However, whereas the majority of sporadic breast tumors that stained negative for p53 accumulation had wild-type TP53, the majority of BRCA1-associated breast tumors that stained negative for p53 accumulation had protein-truncating TP53 mutations (nonsense, frameshift, and splice mutations). Therefore, the strong selection for p53 loss in BRCA1-related tumors is achieved by an increase of protein-truncating TP53 mutations rather than hotspot mutations. Hence, immunohistochemical detection of TP53 mutation could lead to misdiagnosis in approximately half of all BRCA1-related tumors. The presence of deleterious TP53 mutations in most, if not all, BRCA1-related breast cancers suggests that p53 loss of function is essential for BRCA1-associated tumorigenesis. BRCA1-related tumors may therefore be treated not only with drugs that target BRCA1 deficiency [e.g., poly(ADP-ribose) polymerase inhibitors] but also with drugs that selectively target p53-deficient cells. This raises interesting possibilities for combination therapies against BRCA1-deficient breast cancers and BRCA1-like tumors with homologous recombination deficiency.

Expression of the multidrug resistance protein MRP and the lung-resistance protein LRP in nasal NK/T cell lymphoma: further exploring the role of P53 and WT1 gene

Nasal NK/T-cell lymphoma (NKTL) is relatively common in the adult men of Asia. Many patients with nasal NKTL have poor response to therapy. Some of them show P-glycoprotein over-expression. To investigate the expression of other multidrug resistance proteins (MDR) and possible regulatory factors in nasal NKTL, the clinical and pathological features are described. Thirty Chinese adults with nasal NKTL are presented. Immunohistochemical study was carried out to detect multidrug resistance-associated protein 1 (MRP) and lung resistance-related protein (LRP). The association between possible regulatory proteins (P53 and WT1) and MDR were explored. In situ hybridisation for Epstein-Barr virus (EBV) detection, polymerase chain reaction assay for T-cell receptor gene and direct sequencing for the P53 gene were performed. Seven (23.3%) and eight (26.7%) patients showed immunoreactivity of MRP and LRP, respectively. Positive staining for both markers was identified in 6.7% (2 cases). The EBV was detected in most cases (97%). Twenty-six (86.7%) cases expressed positive nuclear staining of P53. However, of the cases analysed for P53 mutation, none showed a mutaion at the hot spots studied. WT1 protein was not detected in the nasal NKTL. Our study reports expression of MRP and LRP in nasal NKTL. The over-expression of P53 is probably associated with high incidence of EBV infection and unlikely a regulatory protein for the expression of MRP and LRP. Further studies are necessary to validate the association between P53 mutation and expression of MRP and LRP in nasal NKTL.

Clinical Significance of p53 and Ki-67 Expression in Colorectal Cancer

Purpose: This study aimed to evaluate the clinical significance of p53 and Ki-67 expressions in patients with colorectal cancer. Methods: Immunohistochemical expressions of p53 and Ki-67 in 205 patients with colorectal cancer were examined. Results were correlated with clinical and pathological parameters. Results: Overexpression of p53 was significantly associated with a proximal location of the tumor (P=0.031) and with lymph node involvement (P=0.030); however, Ki-67 expression was not correlated with any of the clinicopathological variables. Positive p53 staining was significantly associated with a higher level of Ki-67 (P=0.009). Conclusion: Overexpression of p53 was strongly correlated with lymph node metastasis in colorectal cancer; thus, p53 may be used as a possible prognostic marker in patients with colorectal cancer.

Low Frequency of Epstein Barr Virus Association and High Frequency of p53 Overexpression in an Argentinean Pediatric T-Cell Lymphoma Series

T-cell non-Hodgkin's lymphomas (NHLs) represent 10% to 15% of all diagnosed lymphomas in Western countries. Various geographic frequencies of T-cell NHL have been documented, in part reflecting increased exposure to pathogenic factors such as Epstein-Barr virus (EBV). Our aims were to assess EBV and p53 expression in Argentine pediatric T-cell lymphoma and to correlate them with patients' survival. Epstein-Barr encoded RNAs (EBERs) in situ hybridization and LMP1 and p53 immunohistochemical staining were performed on formalin-fixed paraffin-embedded lymph node biopsies from 25 pediatric T-lymphoma patients. In 17 of 25 samples good-quality DNA was obtained, and EBER polymerase chain reaction was assessed to confirm in situ hybridization and immunohistochemical results. Epstein-Barr virus expression was found in 8.0% of cases. p53-positive staining was distributed in 92% of pediatric cases. Kaplan-Meier survival analysis showed that neither EBV nor p53 expression was statistically significantly associated with event-free survival. Our data showed a low frequency of EBV association with pediatric T-cell lymphoma. It seems that p53 plays an important role in proliferation in our studied population, since it is overexpressed in 92% of T-cell lymphoma cases.

Correlation between Angiogenesis and p53 Expression in Lung Adenocarcinoma of Young Patients

Lung cancer commonly occurs in individuals who are 60 years of age or older. Lung cancer in patients younger than 40 years of age is rare and is often advanced when discovered. However, the biological features of lung cancer in young adults have not yet been fully elucidated. This study was conducted to determine the role of p53 expression and neoangiogenesis in lung adenocarcinomas of young patients. Lung adenocarcinomas, which were surgically resected from 20 patients younger than 40 years of age between 1977 and 1996, were compared with lung adenocarcinomas selected with random sampling from 45 patients older than 60 years of age. The expression of p53, vascular endothelial growth factor (VEGF), CD34, a marker for vascular endothelial cells, and proliferating cell nuclear antigen (PCNA) were studied immunohistochemically in both young and elderly patient groups. Lung adenocarcinomas with p53-positive staining showed higher expression of VEGF protein than p53-negative tumors in both the young and the elderly groups. However, the intratumoral microvessel count was significantly higher in the p53-positive young group than in the elderly group. The percentage of VEGF-positive cells correlated significantly with intratumoral microvessel counts in the young group. The survival rate tended to be poorer in patients with a high VEGF labeling index and p53-positive staining than in other young patients. Lung adenocarcinoma occurring in young patients tends to have a poorer prognosis, and angiogenesis of lung adenocarcinoma in young patients is more closely correlated with p53 expression than in elderly patients.

The Potential Value of EGFR and P53 Immunostaining in Tumors of the Urinary Bladder

The expression of EGFR and p53 has not been adequately studied as a prognostic tool in urinary bladder tumors. We analyzed 74 bladder cancer samples from Egypt for EGFR and p53 expression using immunohistochemistry. The tumors were of different histological types, grades and clinical stages, and with established lymph node status. Almost 61% of the tumors showed positive membranous EGFR expression and 74.3% had positive nuclear staining of p53. Analysis of correlation of the IHC staining with clinical variables showed a significant correlation only between EGFR expression and histological type (p=0.002, ANOVA), in that the expression was higher in squamous cell carcinomas than in other histological types. There were no significant correlations between p53 or EGFR with the other clinicopathological variables, including age, sex, staging, grading, and lymph node status. Further studies are needed to determine if EGFR and p53 might be used as prognostic tools in bladder cancer.

Immunohistochemistry and K‐ras sequence of pancreatic carcinosarcoma

Herein is presented a case of carcinosarcoma of the pancreas in an 82-year-old woman, analyzed on immunohistochemistry and K-ras sequence. The tumor, which arose in the pancreas head, was removed on pancreaticoduodenectomy. The patient died, however, of disseminated intravascular coagulation syndrome from postoperative sepsis 13 days later. Microscopically, the tumor consisted of malignant epithelial (well-differentiated adenocarcinoma cells) and mesenchymal (spindle-shaped tumor cells) components. The adenocarcinoma cells had positive immunostaining for cytokeratin AE1/AE3, cytokeratin 7, epithelial membrane antigen (EMA), CEA and carbohydrate antigen 19-9 (CA 19-9), while focal staining of these proteins was observed in the sarcomatous cells. In contrast, the sarcomatous cells had diffuse immunostaining for vimentin, CD10 and p53, while these proteins were not expressed in the ductal adenocarcinoma cells. These findings support the dual characteristics of a carcinosarcoma. DNA sequencing of the present case indicated point mutations of K-ras in both codons 12 and 34 on exon 2. The latter mutation is likely to correlate with the sarcomatous characteristics of this tumor. The tumor cells had specific and diffuse positive staining for CD10 and p53, with features characteristic of rapid growth.

Granular Cell Tumor of the Esophagus

Purpose: 24 y.o. female referred for 10-month history of emesis and abdominal pain underwent EGD revealing a white-yellow submucosal growth at 32 cm from the incisors measuring 1 cm in length and 0.5 cm in width. Pathology report read: “One fragment consists of pink-staining granular cells with small, rounded nuclei consistent with granular cell tumor (GCT). Cells are strongly positive for S-100 and vimentin. Features of malignancy are absent”. Methods: Abrikossoff first described “granular cell myoblastoma” in 1926. It was considered a myogenic tumor until Fisher and Wechsler's 1962 challenge. Using electron microscopy and Wallerian degeneration studies, they noted similarities between a myoblastoma cell and a degenerating Schwann cell. Today, most pathologists and oncologists acknowledge the neural origin of GCTs supported by positive IHC staining for CD68, Ki-67 (slightly), NKI/C3, NSE, nestin, p53 (slightly), S-100 protein, and vimentin. In addition, positive PAS stain with resistance to diastase digestion and nonreactivity to HHF35, desmin, and alpha-smooth muscle actin are characteristic. Results: GCTs comprise only 0.03% of all tumors, and GI GCTs are even more rare with the distal 1/3 of esophagus cited most frequently. Mean age of diagnosis is 45 years with equal M:F ratio. Dysphagia is the most common symptom correlating to >1 cm size. Classic appearance is a small, non-tender, broad-based, submucosal growth resembling a “molar tooth” when central depression exists. A rubbery or firm consistency is characteristic with pinktan, gray-white, or white-yellow coloration. EUS reveals a homogenous, hypo/isoechoic submucosal lesion. Approximately 200 cases have been documented. Conclusion: GCTs are notoriously benign, but no management guidelines exist. Presently, an esophageal GCT > 2 cm size, symptomatology, interval growth, recurrence, tissue invasion, or advanced histologic/sonographic features prompt resection. Preoperative EGD re-evaluation with confirmatory biopsy followed by EUS to address muscularis and lymphatic invasion are recommended. EMR, Nd:YAG laser ablation, and APC are safe, effective alternatives to surgery in the absence of muscularis or lymphatic involvement. Esophageal GCTs are not radiosensitive, but recurrence is uncommon.Figure: Cells with granular, pink-staining cytoplasm and small nuclei.

Predictive value of MRP2, p53, bcl2 and topoisomerase II immunostainings for the efficacy of anthracyclines-based adjuvant chemotherapy in breast cancer: Results from two randomized trials

616 Background: The identification of predictive biomarkers for the efficacy of adjuvant treatments could allow to better tailor adjuvant treatments. We evaluated the predictive value of MRP2, bcl2, topoisomerase IIα (Topo IIα) expression and p53 status for the efficacy of adjuvant anthracyclines (A)-based chemotherapy. Methods: Tumor samples from 823 patients included at Institut Gustave Roussy (IGR) in two randomized trials comparing an A-based chemotherapy with no treatment were used to perform a tissue-array. Chemotherapy consisted of 5FU (500mg/m2), farmorubicine (90% of patients) or doxorubicin (50 mg/m2) and cyclophosphamide (500 mg/m2) (D1=D28) for 6 cycles. Immunostainings (cut-off: >10% stained cells) were performed for MRP2 (M2III-6; 1:300; Alexis), p53 ( DO-7; 1:50; Dako), bcl2 (124; 1:50; Dako), and Topo IIα (KI-S1; 1:5000; Chemicon). We previously reported predictive values of ER, HER2 expression and molecular subclassification using the same tissue-array (Conforti, Annals of Oncology, 2007). Results: After a median follow-up of 10 years, 174 patients (22%) have presented a relapse and 186 patients (24%) died. Chemotherapy improved DFS (HR = 0.77, 95% CI: 0.63- 0.9), but not OS (HR = 0.88, 95% CI: 0.66–1.1). A positive staining for MRP2, p53, Topo IIα and bcl2 was observed in 122 (16%), 157 (20%), 267 (35%) and 251 (34%) assessable samples respectively. P53 and Topo IIα were more frequently expressed in patients with basal-like (51% and 53%) or HER2-overexpressing tumors (44% and 57%), as compared to other groups (HER2- and nonbasal BC) (11% and 28%). Bcl2 was more frequently positive in patients with luminal-like breast cancer (47% versus 16%, p<0.01). No significant interaction was observed between the four biomarkers expression and treatment efficacy for both DFS and OS (adjusted p values for interaction ranged between 0.30 and 0.85). Conclusions: In this study, we did not detect significant interaction between MRP2, p53, bcl2 and Topo Iia expressions and treatment efficacy. Nevertheless, such study cannot exclude a possible interaction with a higher number of events or different methods (DNA sequencing for p53 mutations and lower dilution [1:200] for S1 Ab). No significant financial relationships to disclose.

Expression of Mina53 and its Significance in Gastric Carcinoma

To study the expression of Mina53 and its relationships with clinicopathological characteristics, antioncogene inactivation and tumor proliferation in human gastric carcinoma, and to explore the role of Mina53 in carcinogenesis and tumor progression. Expression of Mina53 and proliferating cell nuclear antigen (PCNA) was determined in gastric carcinoma (n=79), gastric dysplasia (n=21) and normal gastric tissues (n=20), while p53 was measured in gastric carcinoma tissues by immunohistochemistry. Mina53 was negatively expressed in all normal mucosa tissues. Dysplasia specimens showed weakly positive staining for Mina53 in 3 of 21 cases. Elevated expression of Mina53 was observed in 72 (91.1%) of the gastric carcinomas. No significant associations were found between Mina53 and clinicopathological characteristics such as sex, age, histological differentiation, distant metastasis and lymph node metastasis (p>0.05). There was a significant association with depth of invasion (X2=5.385, p<0.05) and TMN stage (X2=6.255, p<0.05). In gastric carcinoma, positive staining for p53 was detected in 53 of 79 cases (67.1%), showing a significant association with Mina53 (X2=5.161, p<0.05). The mean (+/- SD) PCNA labeling index for gastric carcinoma was 39.47+/-16.92%. Mina53 expression was positively associated with PCNA level (r=0.756, p<0.01). Mina53 was overexpressed in gastric carcinoma and associated with tumor proliferation and antioncogene inactivation. Mina53 could therefore play an important role in the carcinogenesis and progression of gastric carcinoma.