Biomedical subjects

Holger Moch

Publications and source records attributed to Holger Moch.

At least 19 recordsLinked to original sources

PubMed2026

Molecularly Guided Therapy Versus Continued Chemotherapy in Unfavorable Cancer of Unknown Primary: Updated Efficacy and Safety From the Randomized, Phase II CUPISCO Study.

CUPISCO (ClinicalTrials.gov identifier: NCT03498521) demonstrated longer progression-free survival (PFS) with comprehensive genomic profiling (CGP) and subsequent molecularly guided therapies (MGTs), versus standard platinum-based chemotherapy, in patients with previously untreated, unfavorable cancer of unknown primary (CUP) who reached disease control after induction chemotherapy (three cycles). We report efficacy and safety after >1 year of additional follow-up. Eligible patients were randomly assigned (3:1) to MGT (investigator-chosen after discussion in a molecular tumor board) or three further cycles of chemotherapy. The primary end point was PFS. Secondary end points included overall survival (OS) and safety. At data cutoff (December 6, 2024), 436 patients were randomly assigned (326 to MGT; 110 to chemotherapy). Median follow-up was 37.0 months (range, 0.0-67.8). Updated median PFS was 6.1 months (95% CI, 4.7 to 6.5) with MGT and 4.4 months (95% CI, 4.2 to 6.4) with chemotherapy (hazard ratio [HR], 0.75 [95% CI, 0.59 to 0.95]; P = .017); median OS was 15.2 months (95% CI, 13.9 to 18.4) and 12.8 months (95% CI, 9.8 to 15.4), respectively (HR, 0.79 [95% CI, 0.61 to 1.02]; P = .0689). No new safety signals were identified. These updated results aligned with the primary analysis, demonstrating the benefit of CGP with subsequent MGT and highlighting the importance of incorporating CGP at initial diagnosis to guide treatment decisions for patients with unfavorable CUP.

Journal Article↗

PubMed2026

Deep visual multi-omics profiling links morphology and molecular programs in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma exhibits striking intra-tumoral heterogeneity at morphological and genetic levels, complicating treatment and contributing to disease progression. CcRCCs with rhabdoid differentiation are highly aggressive tumors characterized by distinct histopathologies. However, the relationship between morphology, underlying molecular alterations, and tumor behavior remains largely unclear. Here, we present Deep Visual Multi-Omics, an approach integrating digital pathology, morphology-guided single-cell isolation, and ultra-sensitive multi-omics profiling to link cell morphologies to their molecular underpinnings. Across five tumors, we profiled ~40,000 AI-classified and expert-curated cells. We identified progressive molecular dysregulation across cells with increasing histopathological grade coexisting within heterogeneous tumors as well as distinct molecular alterations associated with aggressive rhabdoid ccRCC cells, including signatures consistent with enhanced FOXM1-driven proliferation, altered cell-matrix interactions, and a putative immunomodulatory phenotype. Notably, rhabdoid cells exhibited elevated expression of IFN-beta, PD-L1, CD38, ITGB2, and integrin signaling, suggesting that they themselves may act as a source of signals influencing the local immune microenvironment. Besides providing new insights into the biology of ccRCC and highlighting avenues for future translational studies, this illustrates the potential of Deep Visual Multi-omics to dissect cancer heterogeneity and characterize high-risk cell populations.

Humans↗

PubMed2006

Melanocyte differentiation antigen RAB38/NY-MEL-1 induces frequent antibody responses exclusively in melanoma patients.

Expression pattern and immunogenicity are critical issues that define tumor antigens as diagnostic markers and potential targets for immunotherapy. The development of SEREX (serological analysis of recombinant expression libraries) has provided substantial progress in the identification of tumor antigens eliciting both cellular and humoral immune responses in cancer patients. By SEREX, we have previously identified RAB38/NY-MEL-1 as a melanocyte differentiation antigen that is highly expressed in normal melanocytes and melanoma tissues but not in other normal tissues or cancer types. In this study, we further demonstrate that RAB38/NY-MEL-1 is strongly immunogenic, leading to spontaneous antibody responses in a significant proportion of melanoma patients. The immune response occurs solely in malignant melanoma patients and was not detected in patients with other diseases, such as vitiligo, affecting melanocytes. Fine analysis of the spontaneous anti-RAB38/NY-MEL-1 antibody response reveals a polyclonal B cell recognition targeting various epitopes, although a dominant immunogenic region was preferentially recognized. Interestingly, our data indicate that this recognition is not rigid in the course of a patient's response, as the dominant epitope changes during the disease evolution. Implications for the understanding of spontaneous humoral immune responses are discussed.

Antibodies, Neoplasm↗

PubMed2006

Overexpression of epithelial cell adhesion molecule (Ep-CAM) is an independent prognostic marker for reduced survival of patients with epithelial ovarian cancer.

OBJECTIVE: Currently available clinical and molecular factors provide still an insufficient prognostic and predictive assessment for patients with epithelial ovarian cancer (EOC). To identify a potential molecular target and prognostic/predictive factor for EOC, we investigated in a retrospective study the prognostic value of Ep-CAM overexpression in EOC. METHODS: We assessed by immunohistochemistry the expression of the Ep-CAM antigen on tissue microarrays containing paraffin-embedded tissue samples of 199 patients with documented EOC. Patients were operated for ovarian cancer in the period between June 1980 and January 2000. RESULTS: We observed a rate of Ep-CAM overexpression of 68.8%. Ep-CAM overexpression was significantly related to a decreased overall survival (P = 0.036). The prognostic power of Ep-CAM overexpression was particularly strong in patients with stage III and IV disease. In fact, in this subgroup, median overall survival was twofold higher in patients without as compared to patients with Ep-CAM overexpression (46 vs. 23 months, P < 0.01). Univariate analysis revealed a correlation with histologic grade. We observed a significantly higher rate of Ep-CAM overexpression (83.5%) in grade 3 tumors. Histologic subtypes associated with a higher rate of Ep-CAM overexpression were serous carcinoma, squamous cell carcinoma, undifferentiated carcinoma, clear cell carcinoma, and endometrioid carcinoma. Cox regression analysis showed Ep-CAM overexpression to be an independent prognostic marker (P = 0.037, RR = 1.64). CONCLUSIONS: This retrospective analysis demonstrates for the first time an independent prognostic value of Ep-CAM overexpression in patients with EOC. Ovarian cancer patients with Ep-CAM overexpressing tumors are frequent and would qualify for treatment with Ep-CAM-specific immunotherapeutic approaches.

Adult↗

PubMed2006

p16 expression in primary malignant melanoma is associated with prognosis and lymph node status.

Lymph node (LN) status is an important prognostic factor in melanoma patients. p16 expression and proliferation rate (MIB-1) of primary melanomas have been suggested as a marker of metastatic potential. In this study, the correlation of p16 expression and the proliferation rate (MIB-1) with LN status and tumor-specific survival was investigated in primary melanomas. MIB-1 and p16 expression were analyzed by immunohistochemistry in 64 patients with primary cutaneous melanoma. Thirty four nevi were used as control. All patients underwent sentinel lymph node staging. Three different p16 staining patterns were observed: a combination of nuclear and cytoplasmic staining, only cytoplasmic staining and absence of p16 expression. All 34 nevi displayed a nuclear and cytoplasmic p16 staining, whereas p16 was negative in 14 of 64 (22%) melanomas. The level of p16 expression gradually decreased from benign nevi to melanoma without metastasis to melanoma with metastasis. There was a significant correlation between cytoplasmic p16 expression and absence of metastasis (p < 0.05). Death of disease correlated with absence of p16 immunostaining (p = 0.01). MIB-1 expression was not associated with survival. These results confirm the relevance of p16 expression as a prognostic marker in melanoma patients. In addition, it was shown that cytoplasmic immunostaining for p16 in primary melanoma might serve as a predictor of the LN status. Therefore, immunohistochemical evaluation for p16 expression is of potential value for treatment planning in melanoma surgery.

Adult↗

PubMed2006

Preferential nuclear and cytoplasmic NY-BR-1 protein expression in primary breast cancer and lymph node metastases.

PURPOSE: NY-BR-1 is a recently isolated differentiation antigen, which is expressed in normal mammary tissue and in breast cancer. However, current data are based on RT-PCR analysis and nothing is known about the presence of NY-BR-1 on a protein level. We previously generated a monoclonal antibody to NY-BR-1 to study the protein expression of NY-BR-1. METHODS: In our immunohistochemical study, NY-BR-1 was analyzed in normal tissues, various tumor types, 124 primary breast cancers, and 37 paired lymph node metastases. RESULTS: Among normal tissues, NY-BR-1 was present solely in ductal epithelium of the breast. In tumors, carcinoma in situ and invasive carcinoma of the breast were NY-BR-1 positive whereas other tumors and normal tissues were negative. Sixty percent of invasive breast carcinomas were NY-BR-1 positive, displaying cytoplasmic and/or nuclear immunoreactivity. This coexpression was verified by confocal microscopy. Although the monoclonal antibody identified intratumoral heterogeneity, a majority (72%) of NY-BR-1-positive carcinomas revealed immunoreactivity in >50% of the tumor cells. NY-BR-1 expression was more frequent in estrogen receptor-positive and lymph node-negative primary carcinomas (P < 0.05 each) and was more common in grade 1 (77%) than in grade 2 (63%) or grade 3 (50%) carcinomas (P < 0.05). This suggests that NY-BR-1 expression is lost with tumor progression. Forty-nine percent of lymph node metastases were NY-BR-1 positive. CONCLUSION: This study supports the notion that NY-BR-1 is a differentiation antigen of the breast, which is present in normal and tumorous mammary epithelium. The organ-specific expression of NY-BR-1 and its high prevalence in metastases indicate that it could be a valuable target for cancer immunotherapy.

Antigens, Neoplasm↗

PubMed2006

Mutations in the tyrosine kinase domain of the EGFR gene are rare in synovial sarcoma.

The prognosis of patients with synovial sarcomas is poor. New therapeutic strategies, such as target inhibition of the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) with erlotinib and gefinitib, could be effective, because most synovial sarcomas overexpress this protein. In lung cancer, the responsiveness to gefinitib is strongly related to the presence of mutations in the tyrosine kinase domain of the EGFR gene, while erlotinib sensitivity seems to be partly linked to chromosome 7 polysomy or gene amplification. To clarify the role of EGFR in synovial sarcoma and to explore the potential for a targeted therapy approach, we have examined 13 of these soft tissue tumors. We have analyzed the EGFR expression by immunohistochemistry, searched for polysomy and gene amplification with fluorescence in situ hybridization (FISH) and screened for EGFR mutations in exons 18-21 using PCR and direct sequencing. All 13 tumors showed strong diffuse or focal EGFR expression. No amplifications of the EGFR gene were found. In contrast, several point mutations were identified in exons 18-21 of two synovial sarcomas. Whereas one of these tumors carried only a synonymous mutation, two missense mutations in exons 19 and 21 of the EGFR gene (P733S and A840 T, respectively) could be demonstrated in the second sample. In conclusion, strong EGFR expression in synovial sarcomas is not related to gene amplification. The existence of mutations in the tyrosine kinase domain of the EGFR gene in a small subset of synovial sarcomas suggests that only few patients may profit from the tyrosine kinase inhibitor therapy.

Adolescent↗

PubMed2006

Pancreatic endocrine tumors are a rare manifestation of the neurofibromatosis type 1 phenotype: molecular analysis of a malignant insulinoma in a NF-1 patient.

The tumorigenesis of sporadic endocrine tumors is still not fully understood. It is well known that patients with von Recklinghausen syndrome (NF-1) (OMIM 162200) carrying NF1 germline mutations are predisposed to endocrine tumors including pheochromocytomas and duodenal somatostatinomas. It is unclear, however, whether the rarely reported occurrence of pancreatic insulinomas in NF-1 patients represents a coincidental finding or whether insulinomas are a rare manifestation of the NF-1 syndrome. To determine the potential association between the NF-1 syndrome and pancreatic endocrine tumors, we analyzed a NF-1 patient with a well-differentiated pancreatic endocrine carcinoma for NF1 mutation, allelic loss of the NF1 gene and its expression in peripheral blood and tumor cells. The germline mutation c. 499 del TGTT known in the family was confirmed by polymerase chain reaction (PCR) and direct sequencing of exon 4 in DNA extracted from peripheral blood. Loss of heterozygosity (LOH) analysis of the NF1 gene was carried out using 3 intragenic microsatellite markers on 17q11.2. RNA expression was examined by reverse transcription and a consecutive PCR spanning intron 3 of the NF1 gene including the mutated site in exon 4. Immunohistochemistry was used to analyze NF-1 protein expression. Mutation analysis of peripheral blood leukocytes confirmed the 4 base pair deletion in exon 4 starting at codon 167 (499 del TGTT). LOH analysis of tumor tissue revealed retention of both NF1 alleles. While reverse transcriptase-PCR of peripheral blood showed bi-allelic expression of both the wild-type NF1 and the mutated form, reverse transcriptase-PCR of tumor extracts demonstrated expression of the mutated but not the wild-type NF1 allele. Additionally, neurofibromin, the NF1 gene product, was absent in the tumor tissue of the NF-1 patient. These results show that the wild-type NF1 transcrips and protein are reduced, in the reported insulinoma, supposedly by epigenetic mechanisms. This provides strong evidence that there is a relationship between von Recklinghausen disease and the patient's insulinoma. In this line, insulinomas may be viewed as a rare manifestation of the NF-1 syndrome. Furthermore, the NF1 gene must be considered as a candidate tumor suppressor gene for sporadic insulinomas and probably other pancreatic endocrine tumors.

Base Sequence↗

PubMed2006

Spectrum of epithelial neoplasms in end-stage renal disease: an experience from 66 tumor-bearing kidneys with emphasis on histologic patterns distinct from those in sporadic adult renal neoplasia.

Most (up to 71%) of renal cell neoplasms occurring in patients with end-stage renal disease (ESRD), particularly with acquired cystic disease of the kidney (ACDK), have been reported to be papillary renal cell carcinoma (RCC). Our initial experience with tumors in such a setting indicated that many tumors were histologically difficult to classify into the known subtypes of RCC or had features that were different from those in sporadically occurring RCCs. In this study on 66 ESRD kidneys (52 of which showed features of ACDK) removed because tumors were detected in them, we found two major groups of RCC. Overall, there were 261 grossly identified tumors in these kidneys, and many additional tumors were observed on microscopic evaluation in some. Of the two major groups of RCCs, one consisted of tumors similar to those seen in sporadic settings (ie, clear-cell, papillary, and chromophobe RCC), and these formed the dominant mass in 12 (18%), 10 (15%), and 5 (8%) of the 66 kidneys, respectively. The other group consisted of two subtypes of RCC that appear quite unique to ESRD. The more common tumor that we have designated as "acquired cystic disease-associated RCC" was seen as the dominant mass in 24 (36%) of 66 of the kidneys, and it formed the most common tumor type among the smaller nondominant masses, as well. It was characterized by a typical microcystic architecture, eosinophilic cytoplasm with Fuhrman's grade 3 nuclei, and frequent association with intratumoral oxalate crystals. Additionally, these tumors frequently, but usually focally, exhibited papillary architecture, and clear cytoplasm. These tumors occurred only in kidneys with ACDK, and not in noncystic ESRD. The other category was "clear-cell papillary RCC of the end-stage kidneys," present as the dominant mass in 15 (23%) of the 66 kidneys and occurring in both the ACDK and noncystic ESRD. These predominantly cystic tumors showed prominent papillary architecture with purely clear-cell cytology. Immunohistochemical studies in tumors with histology similar to the known subtypes of sporadic RCC showed immunoprofiles similar to that reported in sporadically occurring tumors. The two subtypes of RCC unique to ESRD had distinctive immunoprofiles supporting their separate morphologic subcategorization. Only the acquired cystic disease-associated RCC showed lymph node metastases in 2 cases and sarcomatoid features in 2 more cases. One of the latter 2 died with widespread metastatic disease within 34 months of nephrectomy. Thus, a broad spectrum of renal cell tumors exist in ESRD, only some of which resemble the sporadic RCCs. Acquired cystic disease-associated RCC is the commonest tumor subtype in ESRD, and biologically it appears to be more aggressive than the other tumor subtypes in ESRD.

Adult↗

PubMed2006

Ultrasonic decalcification offers new perspectives for rapid FISH, DNA, and RT-PCR analysis in bone marrow trephines.

The requisite analyses on bone marrow biopsies are increasing: Molecular analyses such as fluorescence in situ hybridization (FISH), polymerase chain reaction (PCR), and reverse transcriptase (RT)-PCR are demanded in addition to morphology and immunohistochemistry to improve diagnostic accuracy. Moreover, analysis of certain molecular prognostic or predictive biomarkers is increasingly mandatory in the assessment of hematologic diseases. In some circumstances, only formalin fixed, bone-containing tissue is available for molecular analysis. Because various fixation and decalcification procedures can impair DNA and RNA quality, there is an urgent need for standardized decalcification protocols which allow FISH and PCR analysis. In this study we developed a routinely applicable decalcification protocol to optimize the molecular analysis method although preserving morphology and immunohistochemical results. Therefore, we compared 2 different approaches including ultrasonic decalcification versus nonultrasonic procedures and ethylenediaminetetraacetate-based reagents versus acid-based ones. In our hands, the combined use of ultrasound and ethylenediaminetetraacetate-based reagents permits successful interphase FISH, PCR, and RT-PCR analysis whereas concomitantly preserving morphology and antigeneicity.

Biopsy↗

PubMed2006

Uncoupling protein 2 has protective function during experimental autoimmune encephalomyelitis.

Uncoupling protein 2 (UCP2) is a member of the mitochondrial transporter superfamily that is expressed in many tissues, including immune cells. UCP2 prevents oxidative stress by reducing reactive oxygen species. Using UCP2-deficient mice, it was shown that UCP2 is involved in the regulation of insulin secretion, in the resistance to infection, and in atherosclerosis. Here, we investigated the role of UCP2 in experimental autoimmune encephalomyelitis, a murine model of multiple sclerosis. Immunized C57BL/6J UCP2-deficient mice showed a slightly delayed onset during experimental autoimmune encephalomyelitis (13.0 +/- 0.6 versus 11.5 +/- 0.8 in wild-type controls) and developed significantly higher disease scores than littermate controls (maximum disease score of 2.9 +/- 0.2 versus 1.7 +/- 0.2, P = 0.001). Higher levels of infiltrating T cells into the spinal cord meninges and parenchyma were observed. The T-cell proliferative response to the specific antigen was increased in UCP2-deficient mice compared with littermate controls, and CD4 cells of UCP2 knockout mice produced significantly higher levels of pro-inflammatory cytokines, eg, tumor necrosis factor-alpha and interleukin-2, resulting from a Th1 response. Mice lacking UCP2 also developed a higher B-cell response. Concomitantly, CD4 and CD8 cells of the UCP2-deficient mice showed increased production of reactive oxygen species. These results suggest a protective function of UCP2 in chronic inflammatory diseases such as multiple sclerosis.

Animals↗

PubMed2005

Etiology of solitary extrapulmonary positron emission tomography and computed tomography findings in patients with lung cancer.

PURPOSE: The aim of this prospective study was to assess the incidence and the nature of solitary extrapulmonary [18F] fluorodeoxyglucose (FDG) accumulations in patients with non-small-cell lung cancer (NSCLC) staged with integrated positron emission tomography and computed tomography (PET/CT) and to evaluate the impact on management. PATIENTS AND METHODS: A total of 350 patients with NSCLC underwent whole-body PET/CT imaging. All solitary extrapulmonary FDG accumulations were evaluated by histopathology, further imaging, or clinical follow-up. RESULTS: PET/CT imaging revealed extrapulmonary lesions in 110 patients. In 72 patients (21%), solitary lesions were present. A diagnosis was obtained in 69 of these patients, including 37 (54%) with solitary metastases and 32 (46%) with lesions unrelated to the lung primary. Histopathologic examinations of these 32 lesions revealed a second clinically unsuspected malignancy or a recurrence of a previous diagnosed carcinoma in six patients (19%) and a benign tumor or inflammatory lesion in 26 patients (81%). The six malignancies consisted of carcinoma of the breast in two patients, and carcinoma of the orbit, esophagus, prostate, and non-Hodgkin's lymphoma in one patient each. Benign tumors and inflammatory lesions included eight colon adenomas, four Warthin's tumors, one granuloma of the lower jaw, one adenoma of the thyroid gland, one compensatory muscle activity due to vocal chord palsy, two occurrences of arthritis, three occurrences of reflux esophagitis, two occurrences of pancreatitis, two occurrences of diverticulitis, one hemorrhoidal inflammation, and one rib fracture. CONCLUSION: Solitary extrapulmonary FDG accumulations in patients with newly diagnosed lung cancer should be analyzed critically for correct staging and optimal therapy, given that up to half of the lesions may represent unrelated malignancies or benign disease.

Adult↗

PubMed2005

Identification of quantitative trait loci controlling cortical motor evoked potentials in experimental autoimmune encephalomyelitis: correlation with incidence, onset and severity of disease.

Experimental autoimmune encephalomyelitis (EAE) is a polygenic chronic inflammatory demyelinating disease of the nervous system, commonly used as an animal model of multiple sclerosis. Previous studies have identified multiple quantitative trait loci (QTLs) controlling different aspects of disease pathogenesis. However, direct genetic control of cortical motor evoked potentials (cMEPs) as a straightforward measure of extent of demyelination or synaptic block has not been investigated earlier. Here, we examined the genetic control of different traits of EAE in a F2 intercross population generated from the EAE susceptible SJL/J (SJL) and the EAE resistant C57BL/10.S (B10.S) mouse strains involving 400 animals. The genotypes of 150 microsatellite markers were determined in each animal and correlated to phenotypic data of onset and severity of disease, cell infiltration and cMEPs. Nine QTLs were identified. Three sex-linked QTLs mapped to chromosomes 2, 10 and 18 linked to disease severity in females, whereas QTLs on chromosomes 1, 8 and 15 linked to the latency of the cMEPs. QTLs affecting T-lymphocyte, B-lymphocyte and microglia infiltration mapped on chromosomes 8 and 15. The cMEP-associated QTLs correlated with incidence, onset or severity of disease, e.g. QTL on chromosome 8, 32-48 cM (EAE 31) (LOD 6.9, P<0.001), associated to cMEP latencies in non-immunized mice and correlated with disease onset and EAE 32 on chromosome 15 linked to cMEP latencies 15 days post-immunization and correlated with disease severity. Additionally, applying tissue microarray technology, we identified QTLs associated to microglia and lymphocytes infiltration on chromosomes 8 and 15, which are different from the QTLs controlling cMEP latencies. There were no alterations in the morphological appearance of the myelin sheaths. Our findings suggest a possible role of myelin composition and/or synaptic transmission in susceptibility to EAE.

Animals↗

PubMed2005

Mammotome: less invasive than ABBI with similar accuracy for early breast cancer detection.

We performed a prospective analysis of two consecutive biopsy cohorts investigated by the same team to compare the Mammotome system with the ABBI procedure. From April 1997 to August 2003 a series of 413 nonpalpable mammographic lesions in 387 women (median age 56 years, range 30-84 years) were stereotactically biopsied in the University Hospital of Basel, Switzerland. Until October 1999 the ABBI system was applied exclusively, it was subsequently superseded by the Mammotome device in our clinic. Main outcome measures were accuracy, technical demand, and morbidity. Sensitivity (97.3%/96.8%), negative predictive value (99.2%/98.7%), and diagnostic accuracy (99.4%/99.1%) regarding the detection of malignancy were excellent for both techniques (ABBI/ Mammotome). The Mammotome procedure was faster and less invasive, thus causing significantly less morbidity. The larger specimen obtained by the ABBI procedure resulted in more detailed histology. In conclusion, recommend the Mammotome system as the method of choice for detecting nonpalpable early breast cancer.

Adult↗

PubMed2005

Expression of epithelial cell adhesion molecule (EpCam) in renal epithelial tumors.

EpCam is an epithelial adhesion molecule expressed in a broad range of carcinomas. Clinical trials with specific humanized anti-EpCam antibodies have shown promising results and have been inaugurated in renal cell carcinoma (RCC) therapy. To study the EpCam expression profile, primary renal cell neoplasms as well as corresponding metastases were evaluated by immunohistochemistry in tissue microarrays. EpCam expression in oncocytomas and chromophobe RCCs was determined on conventional large sections. Moderate or strong EpCam expression was found in eighteen percent of clear cell (n=147), 75% of chromophobe (n=12), and 55% of papillary RCCs (n=20), but not in oncocytomas (n=3). On large sections, 90% of chromophobe RCCs (n=20) showed a strong and homogeneous positivity, whereas oncocytomas (n=15) revealed EpCam positivity in single tumor cells or small clusters. Fourteen percent of RCC metastases (n=97) showed EpCam expression. Patients with EpCam expressing clear cell RCC showed a trend toward a better prognosis in a Cox regression analysis including stage, grade, and necrosis. The data suggest EpCam as a potential therapeutic target in a subset of patients with RCC. In addition, expression patterns of EpCam could become a helpful tool in the discrimination of chromophobe RCC and oncocytoma.

Adult↗

PubMed2005

Unusual morphologic features of endometrial stromal tumors: a report of 2 cases.

Endometrial stromal tumors with typical morphology usually do not pose diagnostic problems. However, the finding of unusual morphologic features may be misleading in the final interpretation of these tumors. Herein, we described two endometrial stromal sarcomas discovered in hysterectomy specimens of women 31 and 75 years of age. Features typical of endometrial stromal neoplasia were present in both cases. Additionally, in 1 case, extensive fatty metaplasia as well as smooth and skeletal muscle metaplasia were found; and in the second case, focal bizarre nuclei, smooth muscle differentiation, and fibrous change were present. The differential diagnosis in the first case included cellular intravenous leiomyomatosis/lipoleiomyomatosis with skeletal muscle differentiation; and in the second case, a cellular smooth muscle tumor with bizarre nuclei was considered.

Adult↗

PubMed2005

Axillary recurrence rate in breast cancer patients with negative sentinel lymph node (SLN) or SLN micrometastases: prospective analysis of 150 patients after SLN biopsy.

OBJECTIVE: To assess the axillary recurrence rate in breast cancer patients with negative sentinel lymph node (SLN) or SLN micrometastases (>0.2 mm to 0.2 mm to <or=2 mm) in 12% (27/224) of patients. Adjuvant therapy did not differ between the group of SLN-negative patients and those with SLN micrometastases. After a median follow-up of 42 months (range 12-64 months), 99% (222/224) of evaluable patients were reassessed. While 1 patient with a negative SLN developed axillary recurrence (0.7%, 1/122), all 27 patients with SLN micrometastases were disease-free at the last follow-up control. CONCLUSIONS: Axillary recurrences in patients with negative SLN or SLN micrometastases did not occur more frequently after SLN biopsy alone compared with results from the recent literature regarding breast cancer patients undergoing formal ALND. Based on a median follow-up of 42 months-one of the longest so far in the literature-the present investigation does not provide evidence that the presence of SLN micrometastases leads to axillary recurrence or distant disease and supports the theory that formal ALND may be omitted in these patients.

Adult↗

PubMed2004

Different types of microsatellite instability in ovarian carcinoma.

Microsatellite instability at mono- and dinucleotide repeats is the hallmark of the hereditary non-polyposis cancer syndrome (HNPCC) and is related to deficient DNA mismatch repair. In contrast, a distinct form of microsatellite instability at selective tetranucleotide repeats (EMAST or elevated microsatellite alterations at selected tetranucleotides) was described in several non-HNPCC cancer types. EMAST is probably unrelated to mismatch repair defects. We investigated the frequency of microsatellite instability at mononucleotide, dinucleotide and tetranucleotide repeats in a series of 75 ovarian carcinomas (53 serous and 22 non-serous). Microsatellite analysis was carried out using 5 mono- and dinucleotide markers from the National Cancer Institute Consensus Panel and 6 tetranucleotide markers, which have been reported as frequently unstable in the literature. High frequency of microsatellite instability (MSI-H) at mono- and dinucleotide repeats was observed in 9% and a low frequency (MSI-L) in 21% of serous carcinomas. MSI-H was detected in 4% and MSI-L in 18% of non-serous carcinomas. Nine percent of serous carcinomas showed instability at multiple and 9% at single tetranucleotide loci. All non-serous carcinomas were stable at tetranucleotide loci. In summary, EMAST (e.g., tumors with tetranucleotide instability without concomitant MSI-H) was observed in 13% of ovarian serous carcinomas. All EMAST positive tumors were of advanced stage. We conclude that EMAST occurs as a distinct form of microsatellite instability in ovarian cancer. EMAST seems to be particularly frequent in advanced serous carcinomas. Its clinical significance needs to be investigated.

Carcinoma↗