Digital counting methods were developed to decrease the high intra- and inter-observer variability of immunohistochemical markers such as Ki67, with most presenting a good correlation coefficient (CC). Since Ki67 is one of the major contributors to Oncotype DX, it is conceivable that Ki67 expression and the recurrence score (RS) obtained by the multigene panel are positively correlated. We decided first to test to what extent conventional and digital Ki67 quantification methods correlate in daily practice and, second, to determine which of these methods correlates better with the prognostic capacity of the Oncotype DX test. Both Ki67 evaluations were performed in 89 core biopsies with a diagnosis of estrogen receptor (ER) positive HER2-negative breast cancer (BC). Cases were, thus, classified twice for surrogate subtype: first by conventional analysis and then by digital evaluation. The Oncotype RS was obtained in 55 cases that were subsequently correlated to Ki67 evaluation by both methods. Conventional and digital Ki67 evaluation showed good concordance and correlation (CC = 0.81 (95% CI 0.73–0.89)). The correlation of Oncotype DX risk groups and surrogate derived subtypes was slightly higher for the digital technique (rs = 0.46, p < 0.01) compared to the conventional method (rs = 0.39, p < 0.01), even though both were statistically significant. In conclusion, we show that digital evaluation could be an alternative to conventional counting, and also has advantages for predicting the risk established by the Oncotype DX test in ER-positive BC. This study also supports the importance of an accurate Ki67 analysis which can influence the decision to submit ER-positive HER2-negative BC to prognostic molecular platforms.
Background
Nephrectomy is the management of choice for the treatment of renal tumors. Surgical pathologists primarily focus on tumor diagnosis and investigations relating to prognosis or therapy. Pathological changes in non-neoplastic tissue may, however, be relevant for further management and should be thoroughly assessed.
Methods
Here, we examined the non-neoplastic renal parenchyma in 206 tumor nephrectomy specimens for the presence of glomerular, tubulo-interstitial, or vascular lesions, and correlated them with clinical parameters and outcome of renal function.
Results
We analyzed 188 malignant and 18 benign or pseudo-tumorous lesions. The most common tumor type was clear cell renal cell carcinoma (CCRCC, n = 106) followed by papillary or urothelial carcinomas (n = 25). Renal pathology examination revealed the presence of kidney disease in 39 cases (18.9%). Glomerulonephritis was found in 15 cases (7.3%), and the most frequent was IgA nephropathy (n = 6; 2.9%). Vasculitis was found in two cases (0.9%). In 15 cases we found tubulo-interstitial nephritis, and in 9 severe diabetic or hypertensive nephropathy. Partial nephrectomy was not linked to better eGFR at follow-up. Age, vascular nephropathy, glomerular scarring and interstitial fibrosis were the leading independent negative factors influencing eGFR at time of surgery, whereas proteinuria was associated with reduced eGFR at 1 year.
Conclusion
Our large study population indicates a high incidence of renal diseases potentially relevant for the postoperative management of patients with renal neoplasia. Consistent and systematic reporting of non-neoplastic renal pathology in tumor nephrectomy specimens should therefore be mandatory.
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