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C Poremba

Publications and source records attributed to C Poremba.

At least 37 records · Page 2Linked to original sources

Expression of survivin, YB-1, and KI-67 in sporadic adenomas and dysplasia-associated lesions or masses in ulcerative colitis.

Sporadic adenomas are said to exhibit an orderly growth pattern with a reversal of proliferative and apoptotic cell distribution as compared with normal colonic crypts. Dysplastic polyps of patients with ulcerative colitis (UC) may represent dysplasia-associated lesions or masses (DALM) with a high associated cancer risk, or, alternatively, may represent sporadic adenomas. Histologic criteria to differentiate between sporadic adenomas and DALM have not focused on the balance between cell renewal and cell loss. The expression of the novel anti-apoptosis gene product, survivin, and the proliferation markers, Ki-67 and Y-box binding protein (YB-1), were investigated by immunohistochemical localization in sporadic adenomas and DALM lesions of patients with UC. In adenomas, KI-67 was expressed preponderantly at the luminal aspect of the polyp, whereas its expression was diffuse in DALM. Survivin was detected diffusely in both adenomas and DALM. YB-1 showed positive staining in the deep aspect of adenomatous glands but only to a minor degree at the surface, whereas both deep and diffuse expression patterns of YB-1 were seen in DALM. The authors conclude that DALM and sporadic adenomas exhibit different patterns of cellular proliferation and that molecular markers of cell proliferation, Ki-67 and YB-1, may be useful to distinguish sporadic adenomas from DALM. However, the similar expression of survivin suggests that the underlying mechanisms that regulate apoptotic cell death are uniform in these lesions.

Adenoma↗

Glut-1 expression in dysplastic and regenerative lesions of the colon.

Monosaccaride transporter proteins are responsible for transmembrane transport of monosaccarides into cells. Glucose transporter protein 1 (Glut-1) is most prevalent in the cell membranes of erythrocytes and facilitates transport of glucose in tissues with barrier functions, i.e. blood brain barrier. Expression of Glut-1 in malignant tumors is increased due to increased metabolic need of the proliferating cell populations. In colorectal adenomas and carcinomas, membranous expression of Glut-1 has been associated with higher grade of tumors and decreased survival time. We studied the expression of Glut-1 in dysplastic proliferations of the colon which included sporadic adenomas and dysplasia associated lesions (DALM) in patients with ulcerative colitis and reactive/regenerative proliferations of the colon, including non-dysplastic chronic colitis, acute colitis and ischemia. Two patterns of Glut-1 expression were detected. Most adenomas and DALMs showed at least focal membranous expression of Glut-1. In addition a second staining pattern was recognized which consisted of prominent supranuclear dots. This pattern of staining was not only seen in adenomas and DALM but also in non-dysplastic areas immediately surrounding sporadic adenomas, in regenerative chronic colitis and in areas surrounding acute inflammation. Areas away from dysplasia did not show any positive staining for Glut-1. We conclude that two distinct patterns of Glut-1 expression may be found in colonic epithelial proliferation: membranous staining, associated with dysplasia, and, heretofore not described, supranuclear staining which may be related to Glut-1 expression secondary to expression of specific growth factors and not necessarily related to dysplasia.

Adenoma↗

Telomerase is a strong indicator for assessing the proneness to progression in neuroblastomas.

BACKGROUND: As traditional parameters do not ensure completely accurate prognostic grouping in neuroblastoma (NB), new molecular markers are needed for assessing the individual patient's prognosis more precisely. PROCEDURE, RESULTS, AND CONCLUSIONS: Based on 133 NB, we show that telomerase activity (TA) is a powerful, independent prognostic marker for all stages and is capable of differentiating between good and poor outcome in putative 'favorable' clinical or biological subgroups of NB patients. Analysis of gene and protein expression of telomerase subunits suggests that the presence or absence of TA in NB is strongly correlated with expression levels of both the catalytic subunit hTERT and the internal RNA component (hTR).

Disease Progression↗

[Fulminant necrotizing fasciitis secondary to Crohn's disease].

Necrotizing fasciitis is a life-threatening infection, commonly caused by group A streptococci, which has to be treated by surgical exploration and debridement during the first 24 h. Clinical clues are severe pain, in some cases followed by the appearance of bullous formations, and the detection of gas in the soft tissues by computed tomography or MRI. In addition to that, the infection is characterized by rapid inflammatory progression, producing a highly life-threatening situation. Diagnosis is finally based on surgical exploration obtaining specimens for culture and histopathologic examination. Debridement and exploration, in some cases amputation of the extremity, are indicated as soon as possible. Antibiotic therapy increases efficacy too, but there is no substitute for surgical treatment. Inflammatory bowel disease (Crohn's disease in this case) followed by necrotizing fasciitis is rarely mentioned in the literature. Therapeutic management in a situation of immunosuppression is discussed by illustration of an actual case.

Adult↗

[Establishing a cytogenetic and morphological progression models of invasive breast cancer. Comparative genomic hybridization (CGH) in malignant and premalignant tumors of the female breast].

Ductal carcinoma in situ of the female breast and lobular carcinoma in situ are regarded as precursor lesions of invasive breast cancer. We used comparative genomic hybridization to analyze the genetic relationship between these two types of lesion and invasive breast cancer. The series included 166 patients with ductal or lobular carcinoma in situ and invasive breast cancer. Our results reflect the broad heterogeneity of morphologically different subtypes of invasive and noninvasive breast cancer. The data also provide evidence of multiple genetic pathways of invasive breast cancer associated with different morphological subtypes. In conclusion, we propose a combined model of morphological-genetic progression with various parallel pathways in the pathogenesis of invasive breast cancer.

Breast Neoplasms↗

Clinical relevance of immunohistochemical expression of p53-targeted gene products mdm-2, p21 and bcl-2 in breast carcinoma.

The present study was designed to investigate the clinical/prognostic relevance of immunohistochemical expression of p53-targeted genes mdm-2, p21WAF1 and bcl-2 alone and in combination with p53 for the indirect assessment of p53 gene status in breast cancer. 141 archival breast carcinomas were immunostained, and the putative mutational status of the p53 gene was defined in 21 of them, as a control for immunohistochemistry, using the polymerase chain reaction single-strand conformational polymorphism (PCR-SSCP) analysis. Genetic changes of p53 correlated significantly with p53 protein overexpression (p = 0.01) but did not do so with any of the related molecules. Immunohistochemical p53 status was directly correlated with mdm-2 (p = 0.0001), p21 (p = 0.0004) and inversely with bcl-2 (p = 0.005) expression. bcl-2 proved to be an independent marker of prognosis, p53 only in the group of node-positive carcinomas, whereas bcl-2-/p53+ tumours revealed the worst prognosis. Mdm-2 and p21 expression was of prognostic significance neither alone nor in combination. We conclude that the detection of down-stream regulators of p53 does not increase the efficacy of immunohistochemistry in assessing the functional status of p53 in breast cancer; however, their combined analysis may help to select subgroups of patients at the extremes of risk for recurrence, or those with greater chances for survival.

Adult↗

Preoperative diagnosis of bile duct strictures--comparison of intraductal ultrasonography with conventional endosonography.

BACKGROUND: The accuracy of intraductal ultrasonography (IDUS) and endoscopic ultrasonography (EUS) were compared in diagnosing biliary obstruction and in predicting surgical resectability. METHODS: Fifty-six patients with biliary obstruction were investigated preoperatively with both conventional EUS and IDUS. The ultrasonographic miniprobe was inserted into the bile duct system through the working channel of the duodenoscope during endoscopic retrograde cholangiopancreatography (ERCP). Conventional endosonography was performed with echoendoscopes in a standard technique. Images of endoluminal ultrasonography were prospectively reviewed and compared with intraoperative findings and resection specimen analyses. RESULTS: IDUS exceeded EUS in terms of accuracy (IDUS, 89.1%; EUS, 75.6%; P < 0.002), sensitivity (IDUS, 91.1%; EUS, 75.7%; P < 0.002), specificity (IDUS, 80%; EUS, 75%; NS), and T-staging (IDUS, 77.7%; EUS, 54.1%; P < 0.001). In bile duct carcinomas the accuracy rate for lymph node staging using IDUS (60%) is comparable with that using EUS (62.5%). In pancreatic carcinomas, however, lymph node staging using IDUS (13.3%) is significantly (P < 0.002) inferior to EUS (69.2%). Endoluminal ultrasonography may predict the potential resectability of bile duct tumors (IDUS, 81.8%; EUS, 75.6%; P < 0.002). CONCLUSIONS: IDUS proved to be accurate in preoperative diagnosing and T-staging of malignant biliary strictures, whereas it is not suitable for lymph node staging. IDUS using miniprobes during ERCP exceeds conventional EUS in terms of depiction of bile duct obstruction, diagnostic accuracy, and sensitivity and in the prediction of surgical tumor resectability. Additionally, different to EUS, IDUS can conveniently be performed during ERCP in one and the same session.

Adult↗

Genetic relation of lobular carcinoma in situ, ductal carcinoma in situ, and associated invasive carcinoma of the breast.

AIMS: The mutual relation of lobular carcinoma in situ (LCIS) and ductal carcinoma in situ (DCIS) of the breast, as accepted precursor lesions of invasive breast cancer, is controversial. Because they display genetic heterogeneity, it is not clear how genetically advanced these entities are and what causes the transition to an invasive carcinoma. METHODS: Six cases of LCIS, four of them with associated lobular invasive carcinoma, four cases of intermediately differentiated DCIS with an associated invasive lobular carcinoma, and nine cases of intermediately and poorly differentiated DCIS with associated ductal invasive carcinoma were investigated by means of comparative genomic hybridisation (CGH) after microdissection and immunohistochemical staining of E-cadherin. RESULTS: LCIS was characterised by a low average rate of copy number changes, no evidence of amplifications, and a high rate of gains and losses of chromosomal material at 1q and 16q, respectively. A high degree of genetic homology with well differentiated DCIS was obvious, as reported previously. The cases of intermediately differentiated DCIS with associated lobular invasive components and lobular differentiation revealed striking homologies, and a significant difference of E-cadherin expression. The comparison of preinvasive and invasive breast lesions, irrespective of differentiation within the same patient, revealed no specific alteration that might be associated with invasion. Genetic alterations seen in invasive carcinoma were not necessarily seen in the adjacent precursor lesions. CONCLUSIONS: These results provide strong evidence that invasive breast cancer is a disease with multiple cytogenetic subclones already present in preinvasive lesions. Moreover, specific CGH alterations associated with invasion were not observed. Furthermore, the close genetic association between well differentiated and a subgroup of intermediately differentiated DCIS and LCIS led to the hypothesis that LCIS and a subgroup of DCIS are different phenotypic forms of a common genotype.

Breast Neoplasms↗

Telomerase activity and telomerase subunits gene expression patterns in neuroblastoma: a molecular and immunohistochemical study establishing prognostic tools for fresh-frozen and paraffin-embedded tissues.

PURPOSE: We have recently demonstrated that telomerase activity (TA) is an independent prognostic factor in neuroblastomas. In the present study, the prognostic impact of TA and gene expression of the three major telomerase subunits is evaluated by molecular and immunohistochemical techniques in fresh-frozen and paraffin-embedded tissues. PATIENTS AND METHODS: One hundred thirty-three neuroblastomas of all stages were analyzed for TA. The TA levels of 75 neuroblastoma cases were correlated with gene expression of telomerase subunits hTRT, human telomerase RNA (hTR), and telomerase protein 1 (TP1) by quantitative reverse transcriptase polymerase chain reaction (RT-PCR), using an innovative approach on the LightCycler instrument (Roche Diagnostics, Mannheim, Germany). For selected cases, the applicability of RT-PCR and immunohistochemistry for hTRT expression analysis was investigated in paraffin-embedded tissues. TA and subunit expression patterns were correlated with traditional prognostic indicators and disease outcome. RESULTS: TA was present in a total of 39 (29.3%) of 133 neuroblastomas and in 31 (29.8%) of 104 initial neuroblastomas without cytotoxic pretreatment. TA was significantly correlated with both event-free and overall survival (P <.0001). Furthermore, we found a significant correlation between expression levels of TA and hTRT (P <.0001) as well as hTR (P <.001). Multivariate analysis revealed only TA and tumor stage but not serum lactate dehydrogenase, MYCN amplification, or age at diagnosis as independent prognostic factors. CONCLUSION: The significant correlation with clinical outcome strongly recommends that analysis of TA be incorporated into the clinical investigation of each individual neuroblastoma at the time of diagnosis. Because the mere presence or absence of TA without further quantification is sufficient basis for predicting disease outcome, the telomeric repeat amplification protocol assay could be complemented with but not replaced by analysis of hTRT or hTR expression.

Biomarkers, Tumor↗

Correlation of morphologic and cytogenetic parameters of genetic instability with chromosomal alterations in in situ carcinomas of the breast.

Classification of preinvasive breast disease could be better founded using biologic markers, thereby increasing reproducibility. We studied 57 breast ductal and lobular in situ carcinomas by means of comparative genomic hybridization and correlated these findings with quantitative features such as the mean nuclear area, mitotic index (MI), apoptotic index (AI), and the presence or absence of necrosis. Loss of 8p and gains of 8q and 6q were associated, respectively, with a significantly higher MI and AI, whereas loss of 16q was associated with a lower MI and AI. A significantly higher number of alterations per case were seen in tumors with gains of 6q, 8q, and 17q and tumors with loss of 13q. Loss of 16q and gain of 17q correlated with the absence or presence of necrosis, respectively. Our data clearly demonstrate that distinct cytogenetic changes correlate with phenotypic changes, proliferation, and apoptosis. These data may be used to refine existing classification schemes.

Apoptosis↗

Comparative genomic hybridization of ductal carcinoma in situ of the breast-evidence of multiple genetic pathways.

There is strong evidence that ductal carcinoma in situ (DCIS) represents a precursor lesion of invasive breast cancer. In order to analyse specific chromosomal alterations of DCIS, 38 paraffin-embedded specimens of DCIS and six associated invasive carcinomas were examined by means of comparative genomic hybridization (CGH). Losses of 16q material were seen almost exclusively in well- and intermediately-differentiated DCIS. These two subgroups differed in the average number of genetic imbalances, 2.5 and 5.5 respectively. Additionally, a higher frequency of gains of 1q and losses of 11q material was seen in intermediately-differentiated in contrast to well-differentiated DCIS. Poorly-differentiated DCIS displayed a higher frequency of amplifications (17q12, 11q13) and a higher average rate of genetic imbalances (7.1). Analysis of adjacent invasive breast carcinoma revealed a genetic pattern almost identical to the one seen in the DCIS counterpart. These data characterize DCIS as a genetically far-advanced, heterogeneous lesion and as a direct precursor of invasive breast cancer.

Breast Neoplasms↗

Different genetic pathways in the evolution of invasive breast cancer are associated with distinct morphological subtypes.

Invasive breast cancer shows a wide range of morphological differentiation, associated with differences in prognosis, but as yet, the underlying genetic mechanisms cannot be accounted for. In order to establish a model of the possible progression from the different subtypes of ductal carcinoma in situ (DCIS) to invasive breast cancer, 77 selected cases of invasive breast cancer representing distinct morphological subtypes were investigated by means of comparative genomic hybridization (CGH). There was a high degree of genetic homology between tubular and tubulo-lobular carcinoma and well-differentiated DCIS, and between ductal invasive carcinoma G3 and poorly differentiated DCIS. Highly differentiated invasive breast cancers were characterized by a loss of 16q and a low average number of aberrations per case. In high-grade tumours, losses of this chromosomal region were seen with a much lower frequency in cases with evidence of an aneuploid tumour status. These data demonstrate the close genetic similarity of well-, intermediately, and poorly differentiated DCIS and distinct morphological types of invasive breast carcinoma, providing further evidence that DCIS is a direct precursor lesion of invasive breast cancer and that various evolutionary genetic pathways exist.

Adenocarcinoma↗

Polypoid tumors of the major duodenal papilla: preoperative staging with intraductal US, EUS, and CT--a prospective, histopathologically controlled study.

BACKGROUND: An adenoma-carcinoma sequence also applies to adenomas of the major duodenal papilla. Therefore accurate preoperative diagnosis and tumor staging are essential to select the appropriate patients for adequate treatment. In a prospective, histopathologically controlled study of tumors of the main duodenal papilla, the preoperative diagnostic value of ultrasound (US) catheter probes applied during endoscopic retrograde cholangiopancreatography (ERCP) was investigated. METHODS: Intraductal US was compared with conventional endoscopic ultrasonography (EUS) and computed tomography (CT). In 27 consecutive patients with benign polypoid tumors of the major duodenal papilla (n = 12) and carcinomas of the papilla (n = 15), respectively, the value of these imaging procedures in determining tumor visualization, tumor diagnosis and tumor staging according to the TNM classification was assessed. Every patient underwent surgical resection; histopathologic evaluation of resected specimens served as the reference standard. RESULTS: Intraductal US was significantly superior to EUS and CT in terms of tumor visualization (100% vs 59.3% vs 29.6%, respectively). Sensitivity and specificity rates for intraductal US and EUS were 100% versus 62.5% and 75% versus 50%, respectively. Overall accuracy rate in tumor diagnosis for intraductal US (88.9%; 24 of 27) was significantly (p = 0.05) superior to EUS (56.3%; 9 of 16). The latter did not depict 4 adenomas and 7 carcinomas. Neither intraductal US nor EUS is suitable for detection of distant metastases. CONCLUSION: Intraductal US appears to be the most effective imaging method in visualizing, diagnosing and staging tumors of the major duodenal papilla. Combining ERCP with catheter probe sonography offers a new diagnostic modality that has some potential advantages for local staging of small tumors of the main duodenal papilla. Consequently, minimally invasive techniques for resection of seemingly benign tumors of the papilla or, even more so, of small carcinomas should preferably be based on intraductal US.

Adenocarcinoma↗

Telomerase activity distinguishes between neuroblastomas with good and poor prognosis.

BACKGROUND: Treatment of neuroblastoma has remained a major challenge in pediatric oncology because the assessment of the individual prognosis, particularly in disseminated disease is still obscure. Previous studies have correlated clinical outcome with activity levels of telomerase, a cellular reverse transcriptase which has been detected in the majority of human malignant tumors. PATIENTS AND METHODS: In this blind-trial study, a non-radioactive telomeric repeat amplification protocol (TRAP) with an internal telomerase-assay standard was used on an automated laser fluorescence sequencer for the detection and semiquantitative analysis of telomerase activity (TA) in 67 neuroblastomas of all clinical stages from the German Neuroblastoma Trial and 2 ganglioneuromas. TA levels were correlated with event-free and overall survival rates and established prognostic markers such as MYCN. RESULTS: TA was present in 14 of 69 (20%) samples, including 3 of 22 stage IVS, 8 of 14 stage IV, 1 of 10 stage III, 1 of 7 stage II and 1 of 14 stage I neuroblastomas and 0 of 2 ganglioneuromas. We found a strong statistical correlation between the presence of TA and poor clinical prognosis with regard to all tumor stages. Multivariate analysis revealed TA as an independent prognostic marker. In particular, the analysis of TA in IVS neuroblastomas distinguished two different prognostic groups. CONCLUSIONS: Our data suggest that TA is an independent prognostic marker in neuroblastoma which, in combination with other markers such as MYCN, may proof useful in assessing the individual patient's prognosis.

Amino Acid Sequence↗

Tumors of the papilla of Vater--inadequate diagnostic impact of endoscopic forceps biopsies taken prior to and following sphincterotomy.

BACKGROUND: It has been proposed that adenomas of the papilla of Vater are precursors of adenocarcinomas. Duodenoscopy with ERCP and forceps biopsies have substantially improved the morphologic exploration of the major duodenal papilla. Yet there is little and contradictory information as to the diagnostic accuracy of endoscopic biopsies in tumors of the papilla. Moreover, after endoscopic sphincterotomy data on the diagnostic impact of endoscopic biopsies from the papilla are scarce and, in most cases, retrospectively obtained. Thus, the aim of the present prospective and histopathologically controlled study was to assess the diagnostic accuracy of endoscopic biopsies taken from tumors of the papilla before and after sphincterotomy. PATIENTS AND METHODS: Forty patients with tumors of the papilla of Vater were included in the study. In each case, a comparison was made between endoscopic forceps biopsy diagnoses prior to and following sphincterotomy and the definitive histological diagnosis after surgical tumor resection. RESULTS: Resected tumors were diagnosed histomorphologically as follows: 19 adenocarcinomas (47%), 6 tubular adenomas (15%), 7 villous adenomas (17%), 7 inflammatory non-neoplastic lesions (pseudotumors) (17%), and one adenomyoma (2%). Overall accuracy for preoperative histopathological diagnosis was 62% (25 of 40, 95% CI: 47%-76%) prior to sphincterotomy while it was 70% (28 of 40, 95% CI: 55%-81%) following the procedure. Regarding adenocarcinomas, sensitivity was found to be 21% (4 of 19, 95% CI: 8%-43%) prior to and 37% (7 of 19, 95% CI: 19%-58%) after sphincterotomy while specificity was 100% at both times. CONCLUSIONS: Endoscopic forceps biopsies do not allow for reliable preoperative diagnosis of tumors of the papilla of Vater.

Adenocarcinoma↗

Telomerase is a highly sensitive and specific molecular marker in fine-needle aspirates of breast lesions.

PURPOSE: Telomerase has been detected in a majority of human malignant tumors, making telomerase activity (TA) one key difference between mortal and immortal cells. In this study, we evaluated in blind-trial fashion the association of TA with cytologic and final clinical/pathologic diagnosis in fine-needle aspirates (FNAs) of breast lesions. MATERIALS AND METHODS: In 172 FNAs, including 80 samples that were cytologically malignant, 18 that were atypical but not diagnostic for malignancy, and 74 that were cytologically benign, TA was determined by a modified nonradioactive telomeric repeat amplification protocol (TRAP) assay. Final diagnosis was made by pathologic examination of follow-up surgical material available for all the cytologically malignant samples, a majority of the cytologically atypical samples, and a portion of the cytologically benign samples. RESULTS: TA was detected in 85 of 172 samples. Comparison of the cytologic and histologic diagnoses with TA showed that 80 of 87 samples from patients with breast cancer were telomerase-positive, resulting in a sensitivity of 92%. TA was found in four of five FNAs from carcinomas that were considered cytologically atypical but not diagnostic for malignancy. Eighty of 85 samples from patients with benign breast lesions were telomerase-negative, revealing a specificity of 94%. The five positive cases in this group were all fibroadenomas with low TA. Among the 18 cases with a cytologic diagnosis of atypia, there was a strong positive relationship between TRAP findings and histologic diagnosis. CONCLUSION: The detection of TA in FNAs of breast lesions is a highly sensitive and specific marker of malignancy and may be used as an adjunct in cases with an equivocal cytologic diagnosis.

Biomarkers, Tumor↗