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  • 1
    In: Breast Care, S. Karger AG, Vol. 16, No. 5 ( 2021), p. 523-531
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 PITX2 DNA methylation has been shown to predict outcomes in high-risk breast cancer patients after anthracycline-based chemotherapy. To determine its prognostic versus predictive value, the impact of PITX2 DNA methylation on outcomes was studied in an untreated cohort vs. an anthracycline-treated triple-negative breast cancer (TNBC) cohort. 〈 b 〉 〈 i 〉 Material and Methods: 〈 /i 〉 〈 /b 〉 The percent DNA methylation ratio (PMR) of paired-like homeodomain transcription factor 2 (PITX2) was determined by a validated methylation-specific real-time PCR test. Patient samples of routinely collected archived formalin-fixed paraffin-embedded (FFPE) tissue and clinical data from 144 TNBC patients of 2 independent cohorts (i.e., 66 untreated patients and 78 patients treated with anthracycline-based chemotherapy) were analyzed. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 The risk of 5- and 10-year overall survival (OS) increased continuously with rising PITX2 DNA methylation in the anthracycline-treated population, but it increased only slightly during 10-year follow-up time in the untreated patient population. PITX2 DNA methylation with a PMR cutoff of 2 did not show significance for poor vs. good outcomes (OS) in the untreated patient cohort (HR = 1.55; 〈 i 〉 p 〈 /i 〉 = 0.259). In contrast, the PITX2 PMR cutoff of 2 identified patients with poor (PMR & #x3e;2) vs. good (PMR ≤2) outcomes (OS) with statistical significance in the anthracycline-treated cohort (HR = 3.96; 〈 i 〉 p 〈 /i 〉 = 0.011). The results in the subgroup of patients who did receive anthracyclines only (no taxanes) confirmed this finding (HR = 5.71; 〈 i 〉 p 〈 /i 〉 = 0.014). 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 In this hypothesis-generating study PITX2 DNA methylation demonstrated predominantly predictive value in anthracycline treatment in TNBC patients. The risk of poor outcome (OS) correlates with increasing PITX2 DNA methylation.
    Type of Medium: Online Resource
    ISSN: 1661-3791 , 1661-3805
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2021
    detail.hit.zdb_id: 2205941-6
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  • 2
    In: Pathobiology, S. Karger AG, Vol. 68, No. 1 ( 2000), p. 9-17
    Abstract: The characterisation of the early molecular genetic events of tumor development depends on the selective procurement of histopathologically defined small cell populations from premalignant tissue. In order to obtain high-quality DNA, mRNA and proteins from these small tissue samples and even from single cells, tissue microdissection is one of the most useful techniques, becoming increasingly important for molecular pathologists. Using different microdissection techniques which allow the isolation of morphologically defined cell populations under direct visualisation, it is now feasible to study molecular genetic events that drive the multistep evolution in tumours. This review aims to present the current techniques of tissue microdissection and these techniques are discussed in the light of their ability to isolate premalignant cell populations in particular. Furthermore, we describe the subsequent application of several multiplex molecular analyses for characterising the microdissected premalignant cells. Applying these advanced techniques, alterations in the cellular DNA or the fluctuation of expressed genes that correlate with a particular stage of carcinogenesis can ultimately be compared within or between individual patients. Thus, these new technologies will have an enormous impact on molecular pathology with several diagnostic, prognostic and therapeutic implications.
    Type of Medium: Online Resource
    ISSN: 1015-2008 , 1423-0291
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2000
    detail.hit.zdb_id: 1483541-1
    SSG: 12
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  • 3
    In: Oncology, S. Karger AG, Vol. 101, No. 2 ( 2023), p. 126-133
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 Correct tumor subtyping of primary renal tumors is essential for treatment decision in daily routine. Most of the tumors can be classified based on morphology alone. Nevertheless, some diagnoses are difficult, and further investigations are needed for correct tumor subtyping. Besides histochemical investigations, high-mass-resolution matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) can detect new diagnostic biomarkers and hence improve the diagnostic. 〈 b 〉 〈 i 〉 Patients and Methods: 〈 /i 〉 〈 /b 〉 Formalin-fixed paraffin embedded tissue specimens from clear cell renal cell carcinoma (ccRCC, 〈 i 〉 n 〈 /i 〉 = 552), papillary renal cell carcinoma (pRCC, 〈 i 〉 n 〈 /i 〉 = 122), chromophobe renal cell carcinoma (chRCC, 〈 i 〉 n 〈 /i 〉 = 108), and renal oncocytoma (rO, 〈 i 〉 n 〈 /i 〉 = 71) were analyzed by high-mass-resolution MALDI fourier-transform ion cyclotron resonance (FT-ICR) MSI. The SPACiAL pipeline was executed for automated co-registration of histological and molecular features. Pathway enrichment and pathway topology analysis were performed to determine significant differences between RCC subtypes. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 We discriminated the four histological subtypes (ccRCC, pRCC, chRCC, and rO) and established the subtype-specific pathways and metabolic profiles. rO showed an enrichment of pentose phosphate, taurine and hypotaurine, glycerophospholipid, amino sugar and nucleotide sugar, fructose and mannose, glycine, serine, and threonine pathways. ChRCC is defined by enriched pathways including the amino sugar and nucleotide sugar, fructose and mannose, glycerophospholipid, taurine and hypotaurine, glycine, serine, and threonine pathways. Pyrimidine, amino sugar and nucleotide sugar, glycerophospholipids, and glutathione pathways are enriched in ccRCC. Furthermore, we detected enriched phosphatidylinositol and glycerophospholipid pathways in pRCC. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 In summary, we performed a classification system with a mean accuracy in tumor discrimination of 85.13%. Furthermore, we detected tumor-specific biomarkers for the four most common primary renal tumors by MALDI-MSI. This method is a useful tool in differential diagnosis and biomarker detection.
    Type of Medium: Online Resource
    ISSN: 0030-2414 , 1423-0232
    RVK:
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2023
    detail.hit.zdb_id: 1483096-6
    detail.hit.zdb_id: 250101-6
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