scholarly journals Deep learning approach to predict lymph node metastasis directly from primary tumor histology in prostate cancer

2021 ◽  
Author(s):  
Frederik Wessels ◽  
Max Schmitt ◽  
Eva Krieghoff‐Henning ◽  
Tanja Jutzi ◽  
Thomas S. Worst ◽  
...  
2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5061-5061
Author(s):  
Simpa Samuel Salami ◽  
Daniel H Hovelson ◽  
Romain Mathieu ◽  
Jeremy B Kaplan ◽  
Martin Susani ◽  
...  

5061 Background: Current tissue-based prognostic biomarker assays claim that assessment of a single biopsy focus is sufficient to predict disease behavior. We analyzed and compared the genetic profiles of multifocal prostate cancer (PCa) with concordant lymph node metastasis (LNM) to determine if expression-based prognostic tests are robust to multifocality. Methods: This IRB-approved study comprised patients who underwent radical prostatectomy and lymph node dissection that revealed N1 or discordant multifocal (low- and high-grade foci) disease. DNA and RNA were co-isolated from each tumor focus pre-identified on formalin fixed paraffin embedded specimens. High depth, targeted DNA and RNA next generation sequencing was performed to characterize the molecular profile of each sample, using the Oncomine Comprehensive (11 patients) or Comprehensive Cancer (DNA, 3 patients) Panels and a custom targeted RNAseq panel comprising genes for deriving prognostic signatures. Results: A total of 67 primary tumor and 17 LNM foci from 14 patients were analyzed. We observed significant intra- and inter-patient molecular heterogeneity. For example, in patient #1, while all 4 regions of high-grade primary tumor showed TP53 somatic mutations and some copy number alterations (CNAs) with two samples from the LNM, tumor areas near the positive margin showed more complete concordance than intraprostatic regions. Critically, a low-grade primary tumor focus in this case showed no somatic mutation or CNA overlap with the high-grade or LNM samples. In patient #4, all tumor and LNM foci shared a large number of somatic mutations, including a frameshift mutation in PTEN, with no high level CNA, consistent with a hypermutated genotype. By targeted RNAseq, low- and high-grade tumors from the same patient showed distinct expression profiles using genes included in prognostic signatures. Conclusions: Our results challenge the claim that expression-based prognostic tests are robust to multifocality. Further studies are needed to better characterize the biologically dominant lesion in multifocal PCa and hold promise for the development of improved prognostic biomarkers.


2009 ◽  
Vol 2 (1) ◽  
pp. 16-31
Author(s):  
Sanja Coso ◽  
Elizabeth D. Williams

2021 ◽  
Vol 22 (14) ◽  
pp. 7406
Author(s):  
Ana Amor López ◽  
Marina S. Mazariegos ◽  
Alessandra Capuano ◽  
Pilar Ximénez-Embún ◽  
Marta Hergueta-Redondo ◽  
...  

Several studies have demonstrated that melanoma-derived extracellular vesicles (EVs) are involved in lymph node metastasis; however, the molecular mechanisms involved are not completely defined. Here, we found that EMILIN-1 is proteolyzed and secreted in small EVs (sEVs) as a novel mechanism to reduce its intracellular levels favoring metastasis in mouse melanoma lymph node metastatic cells. Interestingly, we observed that EMILIN-1 has intrinsic tumor and metastasis suppressive-like properties reducing effective migration, cell viability, primary tumor growth, and metastasis. Overall, our analysis suggests that the inactivation of EMILIN-1 by proteolysis and secretion in sEVs reduce its intrinsic tumor suppressive activities in melanoma favoring tumor progression and metastasis.


Urology ◽  
2011 ◽  
Vol 78 (3) ◽  
pp. S318
Author(s):  
S. Robinson ◽  
O. Karim ◽  
M. Laniado ◽  
H. Motiwala

2001 ◽  
Vol 125 (7) ◽  
pp. 921-923 ◽  
Author(s):  
Jiazhong Jiang ◽  
Thomas M. Ulbright ◽  
Cheryl Younger ◽  
Katya Sanchez ◽  
David G. Bostwick ◽  
...  

Abstract Background.—Cytokeratin 7 (CK7) and cytokeratin 20 (CK20) are 2 types of intermediate filament protein. Expression of CK7 is seen in the majority of primary urinary bladder carcinomas. CK20 is restricted to superficial and occasional intermediate cells of the normal urothelium of the bladder. Aberrant CK20 expression has been documented in urothelial carcinoma and has proved useful as an ancillary diagnostic aid for urinary bladder tumor. Our hypothesis is that the pattern of CK7 and CK20 expression in metastatic urothelial carcinoma duplicates the expression of the same markers in the primary tumors. Therefore, immunohistochemical staining of metastatic tumors for these 2 markers may be helpful for differential diagnosis in ambiguous metastatic tumor deposits. Objective.—To determine the concordance of CK7 and CK20 expression in primary bladder urothelial carcinoma and the matched lymph node metastasis. Design.—We studied 26 patients with lymph node metastases who underwent radical cystectomy and bilateral lymphadenectomy for bladder carcinoma. Immunohistochemical staining for CK7 and CK20 was performed on formalin-fixed paraffin-embedded tissues containing primary cancers and lymph node metastases. Results.—In all cases, there was a concordant expression of CK20 in the primary cancer and its matched lymph node metastasis. Twelve cases (46%) showed positive CK20 immunoreactivity in the primary tumor and its matched lymph node metastases, whereas 14 cases (54%) were negative for CK20 in both the primary tumor and lymph node metastasis. All cases showed positive CK7 immunoreactivity in the primary cancers and matched lymph node metastases. Conclusions.—CK20 immunoreactivity is reliably observed in metastases from bladder cancer when the primary tumor expresses CK20.


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