Sentinel lymph node (SN) biopsy is part of the staging procedure in breast cancer patients. In this study, we compared an intraoperative tool named one-step nucleic acid amplification (OSNA) to our routine histological investigation. OSNA consists of a short homogenization step followed by amplification of cytokeratin (CK) 19 mRNA directly from the lysate. To evaluate the performance of OSNA in comparison to histology, analysis of 343 axillary lymph nodes (ALN) from 93 breast cancer patients was performed with both methods. Discordant samples were subjected to other methods. If these tests supported the OSNA results, these samples were excluded from the study. The concordance rate was 91.8%, sensitivity 98.1%, and specificity 90.8% before and 95.5%, 100%, and 95.6%, respectively, after discordant case investigation. Our results show that OSNA is an excellent method for the detection of metastases in lymph nodes and can be applied as an intraoperative diagnostic approach.
Solid pseudopapillary neoplasms of the pancreas almost consistently show a b-catenin mutation activating the Wnt-signaling pathway, resulting in overexpression of cyclin D1, but not in overt malignancy of this tumor. Besides cyclin D1, a set of markers (ie FLI-1, CD56 and progesterone receptor), whose genes map to chromosome 11q, are frequently expressed in solid pseudopapillary neoplasms. Chromosome 11q is a region that is also often affected in pancreatic neuroendocrine tumors. This immunohistochemical study was undertaken to gain insights into the downstream regulation of the Wnt-signaling pathway and the significance of overexpressed gene products belonging to chromosome 11q for the tumorigenesis in solid pseudopapillary neoplasms. Fourteen solid pseudopapillary neoplasms were analyzed for the expression of cyclin-dependent kinase inhibitors p21, p27, p16 and hyperphosphorylated retinoblastoma (pRb) proteins. In an extended series of 93 solid pseudopapillary neoplasms, b-catenin, cyclin D1, FLI-1 and CD56 expression was examined and compared with that in 22 pancreatic neuroendocrine tumors. Solid pseudopapillary neoplasms (98%) showed aberrant expression of b-catenin with a concomitant cyclin D1 expression in 69% of the cases, but no expression of pRb (0%) was found. p27 and p21 were expressed in 100% (14/14) and 86% (12/14) of the cases, but only 2/14 (14%) were positive for p16. FLI-1 was expressed in 63% of solid pseudopapillary neoplasms, but only in 1/22 pancreatic neuroendocrine tumors (5%), cyclin D1 expression was present in 14% of the latter. We conclude that in solid pseudopapillary neoplasms the activated Wnt-signaling pathway is disrupted, and that p21 and p27 are contributing to this fact by blocking of the hyperphosphorylation of the Rb protein, thus causing the very low proliferation rate characterizing the solid pseudopapillary neoplasms. The accumulation of high expression of proteins whose genes are located on chromosome 11q is characteristic of solid pseudopapillary neoplasms, but not of pancreatic neuroendocrine tumors. Modern Pathology (2007) 20, 955-960;
Early lymph node metastasis is common in pancreatic ductal adenocarcinoma (PDAC). The present study has examined the relationship of lymphatic spread to lymph vessel development and the expression of lymphangiogenic cytokines in a series of well-characterized PDACs. The hot spot method revealed the intratumoural and peritumoural lymphatic vessel density (LVD) to be slightly higher in PDACs than in the normal pancreas. The average intratumoural LVD, however, was strikingly decreased. There was no overexpression of vascular endothelial growth factor (VEGF)-C and VEGF-D in PDACs compared with the normal pancreas. LVD and expression of lymphangiogenic cytokines were not related to any of the biological tumour features or to patient survival. Three orthotopic nude mouse PDAC models did not reveal any increase in tumour-associated LVD, despite a high rate of lymph node metastasis. Lymph vessel proliferation was comparable in PDAC and chronic pancreatitis, in both humans and mice. In conclusion, increased lymphangiogenic activity is not required for and does not significantly affect the lymphatic spread of PDAC. The reduced number of human and murine intratumoural lymph vessels indicates that lymphatic metastasis takes place predominantly via peritumoural lymphatic vessels. The weak expression of lymphangiogenic cytokines in neoplastic cells and lymphatic vessel proliferation in peritumoural regions and chronic pancreatitis indicate that inflammation may be the reason for the low rate of lymphangiogenesis.
Adjacent ductal carcinoma in situ (DCIS) is found in approximately 45% of invasive ductal carcinomas (IDC) of the breast. Pure DCIS overexpresses HER2 in approximately 45%. There is uncertainty whether adjacent DCIS impacts on the response to neoadjuvant chemotherapy and trastuzumab as well as whether HER2 expression in IDC component or adjacent DCIS changes throughout treatment. Core biopsies and surgical tissue from participants of the GeparQuattro study with HER2-positive IDC were centrally examined for the area of invasive ductal component and adjacent DCIS before and after receiving neoadjuvant anthracycline-taxane-trastuzumab containing chemotherapy. HER2 overexpression in IDC and adjacent DCIS was quantified separately by immunohistochemistry using the Ventana automated staining system. Pathological complete response (pCR) was defined as no residual invasive or non-invasive tumor tissue. Fifty-nine (37.3%) of 158 IDCs presented with adjacent DCIS at diagnosis. These tumors showed lower regression grades than pure IDC (P = 0.033). The presence of adjacent DCIS was an independent negative predictor of pCR [odds ratio 0.42 (95% CI 0.2-0.9), P = 0.027]. Adjacent DCIS area decreased from pre-treatment to surgery (r = 0.205) with 30 (50.8%) IDCs with adjacent DCIS showing complete eradication of adjacent DCIS. HER2 status of adjacent DCIS was highly correlated with HER2 status of IDC component before (r = 0.892) and after treatment (r = 0.676). Degree of HER2 overexpression of the IDC component decreased in 16 (33.3%) out of 49 patients without a pCR. These 16 IDCs showed lower RGs compared to the 33 IDCs with unchanged HER2 expression (P = 0.055). HER2-positive IDCs with adjacent DCIS is less responsive to neoadjuvant chemotherapy and trastuzumab compared to pure IDC. However, complete eradication of adjacent DCIS is frequently observed. HER2-overexpression of the invasive ductal component decreases in a subset of tumors, which showed less tumor regression.
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