Diagnostic validity of p16, E-cadherin, cyclin D1, p53, and HPV E6/E7 mRNA in CIN 3-like squamous cell carcinoma of the cervix.

Objective: Cervical intraepithelial neoplasia grade 3 (CIN 3)-like SCC is a recently identified deceptive growth pattern that closely mimics endocervical crypt involvement by CIN 3. As CIN 3-like SCC is indistinguishable from endocervical crypt involvement by CIN 3, it poses a significant challenge for pathologists. Method: We examined 23 cases of CIN 3-like SCC, 6 of which also had concomitant conventional invasive SCC, and 9 cases of endocervical crypt involvement by CIN 3 as a control group. Immunohistochemistry was used to investigate the expression of p16, E-cadherin, cyclin D1, and p53, and the expression of human papillomavirus (HPV) E6/E7 mRNA, the key virus carcinogen of HPV, was detected. The clinicopathological, immunohistochemical, and molecular characteristics of endocervical crypt involvement by CIN 3, CIN 3-like SCC, and the concomitant conventional invasive SCC element were examined. Result: CIN 3-like SCC exhibited a characteristic morphology similar to endocervical crypt involvement by CIN 3, with pushing borders invading into the wall of the cervix, often to a significant depth in most cases. Immunophenotypic features of E-cadherin, p16, cyclin D1, and p53 differed between CIN 3-like SCC and conventional invasive SCC, both in staining intensity and region. E6/E7 mRNA expression was higher in CIN 3-like SCC than in endocervical crypt involvement by CIN 3 (P < 0.05). Conclusion: CIN 3-like SCC is the type of cancer, presenting numerous challenges and potential for confusion as it mimics the phenotypes of endocervical crypt involvement by CIN 3.

Re-stratification of patients with copy-number low endometrial cancer by clinicopathological characteristics.

OBJECTIVE: To stratify patients with copy-number low (CNL) endometrial cancer (EC) by clinicopathological characteristics. METHODS: EC patients who underwent surgery between June 2018 and June 2022 at Peking University People's Hospital were included and further classified according to TCGA molecular subtyping: POLE ultramutated, microsatellite instability high (MSI-H), CNL, and copy-number high (CNH). Clinicopathological characteristics and prognosis of CNL patients were retrospectively reviewed. The Cox proportional hazards regression model was applied to perform univariate and multivariate analysis, and independent risk factors were identified. Differentially expressed genes (DEGs) according to overall survival (OS) were screened based on the transcriptome of CNL cases from the TCGA program. Finally, a nomogram was established, with an accuracy analysis performed. RESULTS: (1) A total of 279 EC patients were included, of whom 168 (60.2%) were in the CNL group. A total of 21 patients had recurrence and 6 patients deceased, and no significant difference in recurrence-free survival (RFS) was exhibited among the four molecular subtypes (P = 0.104), but that in overall survival (OS) was statistically significant (P = 0.036). (2) CNL patients were divided into recurrence and non-recurrence groups, and significant differences (P < 0.05) were found between the two groups in terms of pathological subtype, FIGO stage, ER, PR, glycated hemoglobin (HbA1c), and high-density lipoprotein cholesterol (HDL-C). All the above factors were included in univariate and multivariate Cox regression models, among which pathological subtype, PR, and HDL-C were statistically different (P < 0.05), resulting in three independent risk factors for the prognosis of patients in the CNL group. (3) By comparing the transcriptome of tumor tissues between living and deceased CNL patients from the TCGA database, 903 (4.4%) DEGs were screened, with four lipid metabolism pathways significantly enriched. Finally, a nomogram was established, and internal cross-validation was performed, showing good discrimination accuracy with an AUC of 0.831 and a C-index of 0.748 (95% CI 0.444-1.052). (4) According to the established nomogram and the median total score (85.89), patients were divided into the high score group (n = 85) and low score group (n = 83), and the 8 patients with recurrence were all in the high score group. Survival analysis was performed between the two groups, and the difference in RFS was statistically significant (P = 0.010). CONCLUSION: In the CNL group of EC patients, pathological subtype, PR, and HDL-C were independent prognostic risk factors, the nomogram established based upon which had a good predictive ability for the recurrence risk of patients with CNL EC.

Use of Memorial Sloan Kettering Cancer Center nomogram to guide intraoperative sentinel lymph node frozen sections in patients with early breast cancer.

BACKGROUND: We implemented selective use of frozen section (FS) to optimize accuracy and cost control in the intraoperative diagnosis of sentinel lymph node (SLN) in patients with breast cancer, guided by the Memorial Sloan Kettering Cancer Center (MSKCC) nodal metastasis risk prediction nomogram. METHODS: Surgical pathology records were reviewed, examining 2582 consecutive biopsies from 2552 patients with breast cancer to compare intraoperative FS diagnoses with postoperative final reports. We calculated sensitivity, specificity, and false-negative rates (FNRs) for various MSKCC risk levels, also analyzing axillary reoperation rates, with and without FS, and the number needed to treat (NNT) to avoid separate axillary lymph node dissection. RESULTS: The sensitivity, specificity, and FNR of FS were 84.7%, 99.9%, and 15.3%, respectively. FNR and MSKCC risk level negatively correlated (r = -0.86; P = .002). Axillary reoperation rate significantly declined if FS was done (FS: 4.0%; no FS: 36.4%; P = .002). In grouping patients by quartile of MSKCC risk, axillary reoperation rates were 16.7%, 25.1%, 38.7%, and 58.7% without FS, compared with 4.3%, 3.2%, 5.6%, 3.3% with FS and NNT correspondingly fell from 8.1 to 4.6, 3.0, and 1.8. CONCLUSIONS: A stratified decision-making algorithm based on the MSKCC risk prediction model improved the effectiveness of FS during SLN biopsy to avoid axillary reoperation.

Tumor-infiltrating dendritic cells may be used as clinicopathologic prognostic factors in endometrial carcinoma.

OBJECTIVE: To investigate the distribution of dendritic cells (DCs) at different development status in endometrial carcinoma and their relationship with clinical pathology. METHODS: Samples were collected from 95 patients with endometrial endometrioid adenocarcinoma treated in Peking University People's Hospital from 2002 to 2010. Normal endometrial tissue was obtained from 40 women and served as controls. Immunohistochemistry was used to detect the expression of S100-, human leukocyte antigen (HLA)-DR-, and CD1a-positive DCs within the tumor glandular epithelium, the surrounding tumor interstitial tissue, and the equivalent normal endometrial tissue. The relationship of these DCs with clinical stage, pathology grade, myometrial invasion, and lymph node metastasis was analyzed. RESULTS: The rate of S100-positive DCs in the endometrial endometrioid adenocarcinoma glandular epithelium samples from the 95 patients was 48.4% (46/95), and that of the HLA-DR-positive DCs was 27.4% (26/95), which were both significantly higher (P < 0.05) than that in the control group. CD1a-positive DC was rarely expressed in endometrial endometrioid adenocarcinoma glandular epithelium. The rates of the S100- and HLA-DR-positive DCs in tumor interstitial tissue were similar to that of the control group (both, P > 0.05). The proportion of invasion of the S100- and HLA-DR-positive DCs was negatively correlated with the clinical stage and lymph node metastasis but was not correlated with the pathological grade and myometrial invasion. CONCLUSIONS: Dendritic cell invasion was detected in endometrial endometrioid adenocarcinoma. S100- and HLA-DR-positive DCs may have functions related to the delay of tumor progression and lymph node metastasis.