Changes in the tumour microenvironment mark the transition from serous borderline tumour to low-grade serous carcinoma.

Low-grade serous ovarian carcinoma (LGSC) is a rare and lethal subtype of ovarian cancer. LGSC is pathologically, biologically, and clinically distinct from the more common high-grade serous ovarian carcinoma (HGSC). LGSC arises from serous borderline ovarian tumours (SBTs). The mechanism of transformation for SBTs to LGSC remains poorly understood. To better understand the biology of LGSC, we performed whole proteome profiling of formalin-fixed, paraffin-embedded tissue blocks of LGSC (n = 11), HGSC (n = 19), and SBTs (n = 26). We identified that the whole proteome is able to distinguish between histotypes of the ovarian epithelial tumours. Proteins associated with the tumour microenvironment were differentially expressed between LGSC and SBTs. Fibroblast activation protein (FAP), a protein expressed in cancer-associated fibroblasts, is the most differentially abundant protein in LGSC compared with SBT. Multiplex immunohistochemistry (IHC) for immune markers (CD20, CD79a, CD3, CD8, and CD68) was performed to determine the presence of B cells, T cells, and macrophages. The LGSC FAP+ stroma was associated with greater abundance of Tregs and M2 macrophages, features not present in SBTs. Our proteomics cohort reveals that there are changes in the tumour microenvironment in LGSC compared with its putative precursor lesion, SBT. These changes suggest that the tumour microenvironment provides a supportive environment for LGSC tumourigenesis and progression. Thus, targeting the tumour microenvironment of LGSC may be a viable therapeutic strategy. © 2024 The Pathological Society of Great Britain and Ireland.

Vallejos R ，Zhantuyakova A ，Negri GL ，Martin SD ，Spencer SE ，Thornton S ，Leung S ，Lynch B ，Qin Y ，Chow C ，Liang B ，Zdravko S ，Douglas JM ，Milne K ，Mateyko B ，Nelson BH ，Howitt BE ，Kommoss FK ，Horn LC ，Hoang L ，Singh N ，Morin GB ，Huntsman DG ，Cochrane D ... -  《-》

Clinicopathologic and Molecular Features of Paired Cases of Metachronous Ovarian Serous Borderline Tumor and Subsequent Serous Carcinoma.

Chui MH ，Xing D ，Zeppernick F ，Wang ZQ ，Hannibal CG ，Frederiksen K ，Kjaer SK ，Cope L ，Kurman RJ ，Shih IM ，Wang TL ，Vang R ... -  《-》

KRAS (but not BRAF) mutations in ovarian serous borderline tumour are associated with recurrent low-grade serous carcinoma.

BRAF and KRAS mutations in ovarian serous borderline tumours (OSBTs) and ovarian low-grade serous carcinomas (LGSCs) have been previously described. However, whether those OSBTs would progress to LGSCs or whether those LGSCs were developed from OSBT precursors in previous studies is unknown. Therefore, we assessed KRAS and BRAF mutations in tumour samples from 23 recurrent LGSC patients with a known initial diagnosis of OSBT. Paraffin blocks from both OSBT and LGSC samples were available for five patients, and either OSBTs or LGSCs were available for another 18 patients. Tumour cells from paraffin-embedded tissues were dissected out for mutation analysis by conventional polymerase chain reaction (PCR) and Sanger sequencing. Tumours that appeared to have wild-type KRAS by conventional PCR-Sanger sequencing were further analysed by full COLD (co-amplification at lower denaturation temperature)-PCR and deep sequencing. Full COLD-PCR was able to enrich the amplification of mutated alleles. Deep sequencing was performed with the Ion Torrent personal genome machine (PGM). By conventional PCR-Sanger sequencing, BRAF mutation was detected only in one patient and KRAS mutations were detected in ten patients. Full COLD-PCR deep sequencing detected low-abundance KRAS mutations in eight additional patients. Three of the five patients with both OSBT and LGSC samples available had the same KRAS mutations detected in both OSBT and LGSC samples. The remaining two patients had only KRAS mutations detected in their LGSC samples. For patients with either OSBT or LGSC samples available, KRAS mutations were detected in seven OSBT samples and six LGSC samples. Surprisingly, patients with the KRAS G12V mutation have shorter survival times. In summary, KRAS mutations are very common in recurrent LGSC, while BRAF mutations are rare. The findings indicate that recurrent LGSC can arise from proliferation of OSBT tumour cells with or without detectable KRAS mutations.

Tsang YT ，Deavers MT ，Sun CC ，Kwan SY ，Kuo E ，Malpica A ，Mok SC ，Gershenson DM ，Wong KK ... -  《-》

Molecular profiling of low grade serous ovarian tumours identifies novel candidate driver genes.

Hunter SM ，Anglesio MS ，Ryland GL ，Sharma R ，Chiew YE ，Rowley SM ，Doyle MA ，Li J ，Gilks CB ，Moss P ，Allan PE ，Stephens AN ，Huntsman DG ，deFazio A ，Bowtell DD ，Australian Ovarian Cancer Study Group ，Gorringe KL ，Campbell IG ... -  《Oncotarget》

Combination of TP53 and AGR3 to distinguish ovarian high-grade serous carcinoma from low-grade serous carcinoma.

Qiu C ，Wang Y ，Wang X ，Zhang Q ，Li Y ，Xu Y ，Jin C ，Bu H ，Zheng W ，Yang X ，Lu N ，Kong B ... -  《-》