Differences in RRM1 protein expression between diagnostic biopsies and resection specimens, and changes during carboplatin and paclitaxel treatment, in non‐small‐cell lung cancer

Abstract

The substantial discordance between paired samples emphasizes the need for sufficient tumour tissue in biopsies when RRM1 expression is evaluated. No change in RRM1 expression was observed in primary tumours, but expression seemed to be higher in N2 lymph node metastases following chemotherapy. Tumour heterogeneity and potential post-chemotherapy changes should be considered when RRM1 expression is evaluated.

Overexpression of thymidylate synthase (TYMS) is associated with aggressive tumor features and early PSA recurrence in prostate cancer

“…An unfavorable prognosis in prostate cancers with high TYMS expression is not unexpected based on the prognostic impact of TYMS found in various other tumors [ 7 – 10 ] and also based on the established functions of TYMS. Various other genes required for DNA synthesis and structural integrity have been shown to play a role in cancer development and progression, such as for example genes involved in nucleotide synthesis, including thymidine kinase 1 (TK1) [ 30 ] and ribonucleotide reductase M1 (RRM1) [ 31 ], genes involved in DNA synthesis such as DNA polymerases POLA1 [ 32 ], POLQ [ 33 ], and POLE [ 34 ], topoisomerases TOPO1 [ 35 ], TOP2A [ 36 ], and TOP3B [ 37 ], DNA ligases LIG3 [ 38 ] and LIG4 [ 39 ], as well as genes involved in maintenance of DNA structure and integrity, including helicases ATRX [ 40 ], FANCA-Q [ 41 ], RECQL1 [ 42 ], BRIP1 [ 43 ], HELQ [ 44 ], and chromatin modifiers like CHD1 [ 20 ] and CHD5 [ 45 ].…”

Importance of excision repair cross-complementation group 1 and ribonucleotide reductase M1 as prognostic biomarkers in malignant pleural mesothelioma treated with platinum-based induction chemotherapy followed by surgery

“…Age at diagnosis 61 y (59): 20 (17)(18)(19)(20)(21)(22)(23)(24) >61 y (48): 23 (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28) .06 61 y (59): 14 (10-18) >61 y (48): 15 (13)(14)(15)(16)(17) .008y…”

“…Histotype pre-CTX* (19 missing) Epithelioid (55): 23 (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29) Nonepithelioid (33): 13 (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) .003y…”

“…Also in NSCLC studies using the same RRM1 antibody as applied in the present study, changes in RRM1 protein expression after chemotherapy were discovered. 24,25 This may indicate the response of cancer cells toward a resistance phenotype, because it has been reported that RRM1 mRNA level is highly upregulated in acquired gemcitabine-resistant colon cancer cell line continuously treated with gemcitabine in vivo. 26 RRM1 expression analyzed in postchemotherapy tissues did not provide prognostic significance.…”