The conundrum of breast chondrolipoma: Heterotopic, metaplastic, or neoplastic lesion?

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Level of HER2/neu amplification in primary tumours and metastases in HER2-positive breast cancer and survival after trastuzumab therapy

Abstract Background The level of HER2/neu amplification may vary widely in breast cancers with HER2/neu alteration. The clinical significance of this phenomenon is still unclear. This study was aimed to explore the level of HER2/neu amplification in primary tumours and metastases in HER2-positive metastatic breast cancer (MBC) and its potential impact on survival after a trastuzumab-containing therapy. Methods We retrospectively identified MBC patients treated with a trastuzumab-containing therapy and performed dual-colour FISH on tumour samples from either primary tumour and/or metastasis in a central laboratory. Results We retrieved 110 tumour samples from 91 patients and included 79 tumour samples (primary = 56; metastasis = 23) from 63 patients in the final analysis. We found higher level of HER2/neu amplification in the metastases than in the primary tumours (median HER2/CEP17 ratio: 10.5 vs 7.0, respectively). In 69% of patients ( n = 16) with two tumour samples, the level of HER2/neu amplification was higher in the metastasis than in the paired primary tumour (median HER2/CEP17 ratio: 10.9 vs 8.3, respectively, p = 0.004). The incremental gain in level of HER2/neu amplification was associated with significantly shorter OS after trastuzumab-containing therapy ( p = 0.023, HR 1.014, CI95%: 1.002–1.025). Conclusions The level of HER2/neu amplification tends to increase from the primary tumour to the paired metastases in a significant proportion of patients with HER2-positive MBC. This phenomenon, although still not completely understood, could lead to a shorter OS after trastuzumab therapy

Definition of Outcome-Based Prostate-Specific Antigen (PSA) Thresholds for Advanced Prostate Cancer Risk Prediction

We defined prostate-specific antigen (PSA) thresholds from a well calibrated risk prediction model for identifying and excluding advanced prostate cancer (PCa). We retrieved 902 biopsied patients with a pre-biopsy PSA determination (Roche assay). A logistic regression model predictive for PCa including the main effects [i.e., PSA, age, histological evidence of glandular inflammation (GI)] was built after testing the accuracy by calibration plots and Hosmer-Lemeshow test for goodness of fit. PSA thresholds were derived by assuming a diagnostic sensitivity of 95% (rule-out) and 80% (rule-in) for overall and advanced/poorly differentiated PCa. In patients without GI, serum PSA concentrations ≤ 4.1 (<65 years old) and ≤3.7 μg/L (≥65 years old) excluded an advanced PCa (defined as Gleason score ≥ 7 at biopsy), with a negative predictive value of 95.1% [95% confidence interval (CI): 83.0–98.7] and 88.8% (CI: 80.2–93.9), respectively, while PSA > 5.7 (<65) and >6.1 μg/L (≥65) should address biopsy referral. In presence of GI, PSA did not provide a valid estimate for risk of advanced cancer because of its higher variability and the low pre-test probability of PCa. The proposed PSA thresholds may support biopsy decision except for patients with asymptomatic prostatitis who cannot be pre-biopsy identified

Rathke's cleft cyst associated with pituitary granulomatosis with polyangiitis: An unusual combination of hypothalamus-pituitary region pathologies

The authors present an unusual case of a patient suffering from visual deficit due to pituitary granulomatosis with polyangiitis (GPA) associated with Rathke's cleft cyst (RCC). The patient was referred to our Neurosurgery Department presenting right eye amaurosis, third cranial nerve palsy, and left temporal hemianopsia. Magnetic resonance imaging documented a sellar or suprasellar lesion with solid and cystic components. The dura mater of the skull base was also strongly enhanced. The patient underwent surgery. Histologic examination revealed RCC associated with pituitary GPA. To our knowledge, this is the first reported case of concomitant pituitary GPA and RCC. Pituitary involvement in GPA is rare, usually diagnosed in hormonal dysfunctions. The patient in case first presented optic chiasm compression, probably due to inflammation of both the pituitary gland and the previously asymptomatic RCC. We focus on the symptoms that led us to diagnose GPA pituitary involvement and on the peculiar and unusual Magnetic resonance imaging of the case presented

PTEN Expression as a Complementary Biomarker for Mismatch Repair Testing in Breast Cancer

Mismatch repair (MMR) analysis in breast cancer may help to inform immunotherapy decisions but it lacks breast-specific guidelines. Unlike in other neoplasms, MMR protein loss shows intra-tumor heterogeneity and it is not mirrored by microsatellite instability in the breast. Additional biomarkers can improve MMR clinical testing. Phosphatase and tensin homolog (PTEN) inactivation is an early oncogenic event that is associated with MMR deficiency (dMMR) in several tumors. Here, we sought to characterize the diagnostic utility of PTEN expression analysis for MMR status assessment in breast cancer. A total of 608 breast cancers were profiled for their MMR and PTEN status. Proteins expression and distribution were analyzed by immunohistochemistry (IHC) on tissue microarrays and confirmed on full sections; PTEN copy number alterations were detected using a real-time PCR assay. Overall, 78 (12.8%) cases were MMR-heterogeneous (hMMR), while all patterns of PTEN expression showed no intra-tumor heterogeneity. Wild-type PTEN expression was observed in 15 (18.5%) dMMR tumors (p < 0.0001). Survival analyses revealed significant correlations between MMR-proficient (pMMR), PTEN expression, and a better outcome. The positive predictive value of PTEN-retained status for pMMR ranged from 94.6% in estrogen receptor (ER)+/HER2- tumors to 100% in HER2-amplified and ER-/HER2- cases. We propose a novel diagnostic algorithm where PTEN expression analysis can be employed to identify pMMR breast cancers

La Petite presse : journal quotidien... / [rédacteur en chef : Balathier Bragelonne]

29 décembre 18841884/12/29 (A18,N6810)

Level of HER2/neu amplification in primary tumours and metastases in HER2-positive breast cancer and survival after trastuzumab therapy

Abstract Background The level of HER2/neu amplification may vary widely in breast cancers with HER2/neu alteration. The clinical significance of this phenomenon is still unclear. This study was aimed to explore the level of HER2/neu amplification in primary tumours and metastases in HER2-positive metastatic breast cancer (MBC) and its potential impact on survival after a trastuzumab-containing therapy. Methods We retrospectively identified MBC patients treated with a trastuzumab-containing therapy and performed dual-colour FISH on tumour samples from either primary tumour and/or metastasis in a central laboratory. Results We retrieved 110 tumour samples from 91 patients and included 79 tumour samples (primary = 56; metastasis = 23) from 63 patients in the final analysis. We found higher level of HER2/neu amplification in the metastases than in the primary tumours (median HER2/CEP17 ratio: 10.5 vs 7.0, respectively). In 69% of patients ( n = 16) with two tumour samples, the level of HER2/neu amplification was higher in the metastasis than in the paired primary tumour (median HER2/CEP17 ratio: 10.9 vs 8.3, respectively, p = 0.004). The incremental gain in level of HER2/neu amplification was associated with significantly shorter OS after trastuzumab-containing therapy ( p = 0.023, HR 1.014, CI95%: 1.002–1.025). Conclusions The level of HER2/neu amplification tends to increase from the primary tumour to the paired metastases in a significant proportion of patients with HER2-positive MBC. This phenomenon, although still not completely understood, could lead to a shorter OS after trastuzumab therapy