The purpose of this study was to investigate the frequency of microcystic, elongated and fragmented (MELF) pattern of invasion in endometrioid endometrial adenocarcinomas (EA) and its association with prognostic factors. Stained tissue sections from 121 cases of EA (total hysterectomy and pelvic, with or without para-aortic, lymphadenectomy specimens) were reviewed to identify cases showing MELF-type invasion. The prognostic factors of low tumour grade, deep myometrial invasion (MI), cervical stromal involvement, lymphovascular space invasion (LVSI), lymph node (LN) metastasis and advanced clinical stage were more frequently observed in MELF-positive cases (p < 0.05). Thus, MELF-positive cases had an increased frequency (28/121) of these prognostic factors, which has implications in routine clinical practice, as it signals the importance of recognising MELF pattern invasion. In univariate analysis, MELF positivity, deep MI, cervical stroma involvement and LVSI were significantly related to LN metastasis (p < 0.05). However, in multivariate analysis, only MELF pattern invasion and cervical stroma involvement were independent factors for LN metastasis. Nevertheless, further studies are needed to evaluate the clinical significance of MELF pattern of invasion in endometrial adenocarcinoma.
Inherited pathogenic variants account for 5% to 10% of all breast cancer (BC) and colorectal cancer (CRC) cases. Here, we sought to profile the pathogenic variants in 25 cancer susceptibility genes in Turkish population. Germline pathogenic variants were screened in 732 BC patients, 189 CRC patients and 490 cancer-free elderly controls, using next-generation sequencing-based multigene panel testing and multiplex ligation-dependent probe amplification testing. Pathogenic variants were detected in 17.2% of high-risk BC patients and 26.4% of high-risk CRC patients. More than 95% of these variants were clinically actionable. BRCA1/2 and mismatch repair genes (MLH1, MSH2 and MSH6) accounted for two-thirds of all pathogenic variants detected in high-risk BC and CRC patients, respectively. Pathogenic variants in PALB2, CHEK2, ATM and TP53 were also prevalent in high-risk BC patients (4.5%). BRCA1 exons 17-18 deletion and CHEK2 c.592+3A>T were the most common variants predisposing to BC, and they are likely to be founder variants. Three frequent MUTYH pathogenic variants (c.884C>T, c.1437_1439delGGA and c.1187G>A) were responsible for all MUTYH biallelic cases (4.4% of high-risk CRC patients). The total pathogenic variant frequency was very low in controls (2.4%
The objective of this article was to evaluate clinical significance of glandular atypia on Papanicolaou smear, to compare the Bethesda system (TBS) 2001 with the 1991 revision, and to determine whether there is any improvement in the cytohistologic correlation by the new system. Cytology files of 18,955 patients were reviewed for diagnosis of atypical glandular cells of undetermined significance (AGUS), and histopathology files were searched. Cervical smears of these patients were reclassified according to TBS 2001. Of the 18,955 specimens, 89 (0.46%) were diagnosed as AGUS. Of these 89 women, 76 (85.3%) accepted the follow-up protocol of our hospital. In reevaluation according to TBS 2001, 31 specimens were reevaluated as atypical glandular cells (AGC) and 3 were reevaluated as adenocarcinoma in situ, 8 as AGC with concomitant squamous cell abnormalities, 1 as atypical squamous cells that cannot exclude high-grade squamous intraepithelial lesions, and 33 as negative. Thirty-one (93.9%) of these 33 negative cases were in the AGUS-reactive category in the initial examination. The difference between the rates of the malignant pathologies in the AGUS (25%, 19/76) and in the AGC (42.8%, 18/42) categories was significant (chi(2)= 4.0, P= 0.04). The new terminology of AGC is more likely to suggest a clinically significant lesion than TBS 1991. Repeated cytologic testing during follow-up seems to be unacceptable.
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