Dataset Information

Mass spectrometric detection of proteins associated with lymph node metastasis in T1/2 colorectal cancer from FFPE archival specimens

ABSTRACT: Surgical resection of colorectal cancers (CRC) that have not invaded beyond the bowel wall (i.e. Stage I) can achieve 5-year patient survival rates exceeding 90%. In the majority of Stage I cases with T1 (submucosal) or T2 (not beyond the muscularis propria) depth of tumour invasion, surgery alone is curative. However, for approximately 10% of resected T1/2 CRC, even though histopathology inspection of the tumour deems it to be restricted to the bowel wall, malignant cells are identified in draining lymph nodes, signifying local metastasis. These patients are classified with Stage IIIA disease and are at greater risk than Stage I patients whose tumours show similar invasive depth, but lack lymph node involvement. To counter the risk of distant malignant dissemination, Stage IIIA patients require more extensive treatment with adjuvant chemotherapy, while Stage I patients do not. In this study we aim to get a better understanding of the underlying biological pathways linked to lymph node metastasis (LNM) using discovery based MS (DIA) and RNASeq as well as IHC and PRM to verify possible protein marker. All of this was done on archival tissue samples (FFPE).

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Colon

DISEASE(S): Colon Cancer

SUBMITTER: Pascal Steffen

LAB HEAD: Mark P. Molloy

PROVIDER: PXD020808 | Pride | 2021-01-14

REPOSITORIES: Pride

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Publications

Molecular Features of Lymph Node Metastasis in T1/2 Colorectal Cancer from Formalin-Fixed Paraffin-Embedded Archival Specimens.

Steffen Pascal P Li Jun J Chandra Jason J Ahadi Mahsa S MS Gill Anthony J AJ Engel Alexander F AF Molloy Mark P MP

Journal of proteome research 20210111 2

Histological risk factors for lymph node metastasis (LNM) in early-stage colorectal cancers (CRC) have been described, although the predictive utility of these factors varies. Improved LNM risk assessment based on findings in endoscopic colon and rectal excisions is necessary for optimal surgical management of CRC patients with pathologic T1- /T2-staged invasive depth (i.e., tumor not invading beyond the muscularis propria layer); as the current system is overly conservative, and results in many ...[more]

PMID: 33427478

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Project description:Lymph-node (LN) metastases predict for high recurrence rates in breast cancer patients. Eradication of micro-metastatic tumor cells is the primary goal of adjuvant systemic treatment. Decisions regarding systemic treatment depend largely on primary tumor characteristics rather than on characteristics of their LN metastases. However, it remains unclear to what extent LN metastases, having already metastasized locally, resemble their primary breast tumors and as such will be eradicated by the systemic therapy chosen. In this study we investigated the genetic differences between primary breast cancers and their paired LN metastases using array comparative genomic hybridization analyses on a high resolution 720K Nimblegen platform. Thus far, no metastasis-specific genomic aberrations have been identified. We hypothesized that this is due to low-resolution platforms and lack of stratification on breast cancer subtypes (specifically, triple-negative (TN) versus luminal). Furthermore, we speculated that as TN tumours are known to be more genetically unstable, their LN metastases would show an increase in random copy number aberrations (CNAs). Therefore, we studied 10 primary TN breast tumour–LN pairs and 10 luminal pairs and found that all LN metastases clustered nearest to their matched tumour except for two. These two were explained by poor hybridization quality and, interestingly, the presence of two histological components in one tumour. We found no significantly altered CNAs between pairs in the whole group, nor when subdivided over subtypes; neither did we find a CNA increase in LN metastases compared to primary tumours within the TN subgroup, suggesting most CNAs are functional and not random. Our findings suggest a strong clonal relationship between primary breast tumours and its LN metastases and support the use of the primary tumor characteristics to guide adjuvant systemic chemotherapy in breast cancer patients, since primary tumors and their subsequent LN metastases seem remarkably similar, at least prior to treatment. The experiment contains 27 paired primary breast cancer samples with their lymph node metastases, analysed on a 135K whole genome CGH array

Project description:Lymph-node (LN) metastases predict for high recurrence rates in breast cancer patients. Eradication of micro-metastatic tumor cells is the primary goal of adjuvant systemic treatment. Decisions regarding systemic treatment depend largely on primary tumor characteristics rather than on characteristics of their LN metastases. However, it remains unclear to what extent LN metastases, having already metastasized locally, resemble their primary breast tumors and as such will be eradicated by the systemic therapy chosen. In this study we investigated the genetic differences between primary breast cancers and their paired LN metastases using array comparative genomic hybridization analyses on a high resolution 720K Nimblegen platform. Thus far, no metastasis-specific genomic aberrations have been identified. We hypothesized that this is due to low-resolution platforms and lack of stratification on breast cancer subtypes (specifically, triple-negative (TN) versus luminal). Furthermore, we speculated that as TN tumours are known to be more genetically unstable, their LN metastases would show an increase in random copy number aberrations (CNAs). Therefore, we studied 10 primary TN breast tumourM-bM-^@M-^SLN pairs and 10 luminal pairs and found that all LN metastases clustered nearest to their matched tumour except for two. These two were explained by poor hybridization quality and, interestingly, the presence of two histological components in one tumour. We found no significantly altered CNAs between pairs in the whole group, nor when subdivided over subtypes; neither did we find a CNA increase in LN metastases compared to primary tumours within the TN subgroup, suggesting most CNAs are functional and not random. Our findings suggest a strong clonal relationship between primary breast tumours and its LN metastases and support the use of the primary tumor characteristics to guide adjuvant systemic chemotherapy in breast cancer patients, since primary tumors and their subsequent LN metastases seem remarkably similar, at least prior to treatment. The experiment contains 20 paired primary breast cancer samples with their lymph node metastases, analysed on a 720 whole genome CGH array. Additionally, for one sample its two distinct histological subpopulations were analysed on the same platform.

Dataset Information

Mass spectrometric detection of proteins associated with lymph node metastasis in T1/2 colorectal cancer from FFPE archival specimens

Publications

Molecular Features of Lymph Node Metastasis in T1/2 Colorectal Cancer from Formalin-Fixed Paraffin-Embedded Archival Specimens.

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