Pathology International最新文献

The reliability of Ki67-labeling index (LI) in core needle biopsy (CNB) of ER+/HER2- invasive breast carcinoma (IBC) and factors affecting the discordance of Ki67-LI between CNB and surgical resection (SR) remain unsolved. We aimed to elucidate factors influencing the discordance of Ki67-LI between CNB and SR to classify ER+/HER2- IBC into luminal A-like (LumA) and luminal B-like (LumB). The cohort included 326 ER+/HER2- IBCs available with Ki67-LI data at both CNB and SR specimens. Survival analysis was performed on 122 patients. Spearman's rank correlation coefficient of Ki67-LI between them was 0.683. The log-rank test showed that patients with ER+/HER2- IBC with ≥ 20% Ki67-LI at CNB (p < 0.001) and SR specimens (p < 0.001) had significantly shorter disease-free survival. In multivariate analysis, a negative PgR (p = 0.002) and > 2 cm pathological tumor size (p < 0.001) had the most significant effect on the discordance of Ki67-LI between CNB and SR at 20% and 30% cutoffs, respectively. Histological grade III had a significant effect on the concordance between them (p = 0.01) at 20% cutoff. Ki67-LI assessment in CNB may be useful for classifying ER+/HER2- IBC into LumA and LumB with caution of some prognostic factors and cutoffs.

Urinary bladder cancer includes non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC). While patients with NMIBC have a better prognosis, NMIBC often recurs, requiring long-term surveillance and repeated treatments. Intravesical Bacillus Calmette-Guérin (BCG) therapy is standard for high-grade or recurrent NMIBC; however, 30%-50% of patients failed to respond, and the mechanisms of resistance remain unclear. To identify predictive biomarkers for response to intravesical BCG therapy, we analyzed NANOG and Histone deacetylase 1 (HDAC1) expression in 90 bladder cancer specimens from NMIBC patients treated with BCG therapy using immunohistochemistry. The correlation between NANOG and HDAC1 expression and clinical outcomes, including response to BCG therapy, was assessed. High-grade NMIBC cases showed significantly higher expression of NANOG and HDAC1 compared to low-grade cases (p < 0.05). Additionally, elevated NANOG expression in combination with HDAC1, was associated with poor response to BCG therapy and decreased lymphocyte infiltration in the tumor-microenvironment. NANOG is suggested to directly increases HDAC1 expression, which could suppress lymphocyte infiltration in the tumor microenvironment by altering immune-related gene expression. These findings suggest that the NANOG/HDAC1 axis plays a key role in predicting resistance to intravesical BCG therapy in NMIBC.

Pulmonary carcinosarcoma is a rare tumor composed of non-small-cell carcinomas and sarcomatous elements, which is poorly differentiated in most cases. We present a case of carcinosarcoma with a well-differentiated carcinomatous component that required a differential diagnosis from tumors derived from teratomas, such as teratocarcinosarcoma. We present a case of a 68-year-old man who visited our hospital for an examination of a 22-mm lung tumor. The patient underwent left S1+2 segmentectomy, and his postoperative course was uneventful. No recurrence was observed in the 21-month postoperative follow-up period. The segmentectomy specimen revealed a yellow-white, well-circumscribed mass. The tumor consisted of well-differentiated squamous and glandular epithelia, and sarcomatous components of immature spindle cells, chondrosarcoma, and rhabdomyosarcoma. The patient was diagnosed with carcinosarcoma. This case included well-differentiated carcinomatous components, and it was necessary to differentiate it from teratocarcinosarcomas. There was no neural component, and without SMARCA4 loss, which is observed in teratocarcinosarcoma, and ruled out teratocarcinosarcoma. Carcinosarcomas are characterized by a biphasic histopathological pattern, making it difficult to accurately diagnose them on biopsy, which only captures a portion of the tumor. The possibility of carcinosarcoma should be considered even when the tumors derived from teratomas are suspected on preoperative biopsy.

Tumor-infiltrating lymphocyte (TIL) scoring in tumor specimens has gained increasing attention in determining patients who are likely to benefit from immunotherapies. However, the histological evaluation methods of TILs in breast cancer remain limited. This study aimed to assess four components of lymphocytic reaction and overall lymphocytic score (L-score) used in colorectal cancer, investigate its association with clinicopathological factors, and examine the effect of TILs on postoperative mortality using 231 invasive breast cancers without neoadjuvant chemotherapy. Besides L-score, increasing modified L-score lacking peritumoral lymphocytic reaction was significantly associated with aggressive breast cancer phenotypes, including larger invasive size, higher tumor stage, higher Ki-67 labeling index, triple negative and HER2-enriched subtypes, and higher Nottingham histological grade. Importantly, modified L-score status but not L-score or TIL-Working Group (WG) score status was positively correlated with the disease-specific survival rate of the overall patients as well as the patients with luminal type or histological Grade III breast cancers. These results indicated that the modified L-score is a favorable method to comprehensively assess lymphocytic reaction to predict prognosis among patients with breast cancer, even compared with the currently used TIL-WG method, which may possess their potential integration into clinical practice.

Mesothelioma is a highly aggressive tumor affecting an increasing number of patients worldwide. Owing to the poor clinical outcomes associated with current therapies, the development of novel therapies that target cancer stem cells (CSCs) is desirable. Here, we examined the applicability of our previously established hydrogel-based rapid CSC generation method to human mesothelioma cell lines and further analyzed the characteristics of the induced mesothelioma stem cell (MesoSC) -like cells. Human mesothelioma cell lines cultured on hydrogels presented increased expression of pan-stem cell markers and acquired spheroid formation and early tumorigenicity, suggesting that MesoSC-like cells are highly malignant. Microarray analysis demonstrated that the expression of SLC13A5, a citrate transporter involved in TCA cycle, was significantly induced in the resulting MesoSC-like cells. The overexpression of SLC13A5 resulted in a metabolic shift toward oxidative phosphorylation, increased phosphorylation of ERK and YAP, and increased SOX2 expression, leading to increased cisplatin resistance. scRNA-seq database analysis revealed that clinical mesothelioma samples contained a small number of SLC13A5-expressing cells. Our findings suggest that the hydrogel-based CSC generation method is also effective for human mesothelioma cells and that SLC13A5 may contribute to MesoSC survival. The new properties of MesoSCs revealed in this study may provide clues for establishing future treatments.

Squamoid morules are an intriguing finding rarely seen in colorectal adenomas, mimicking foci of microinvasion or neuroendocrine differentiation. We identified nineteen colorectal adenomas with squamoid morules and collected clinicopathological data. A representative block was chosen for immunohistochemistry. The expression of p40, p63, CK5/6, beta-catenin, synaptophysin, chromogranin, and Ki-67 in squamoid morules were examined immunohistochemically. The nineteen patients comprised fifteen males (79%) and four females (21%) ranging in age from 45 to 85 years (average: 59.4 years old). Fourteen adenomas were tubulovillous adenomas (average: 3.4 cm, ranging 1.0 to 6.0 cm) and five were tubular adenomas (average: 2.6 cm, ranging 1.6 to 3.0 cm). All foci of squamoid morules showed beta-catenin nuclear positivity and CK5/6 expression. Squamoid morules were focally positive for p63 in four adenomas and focally positive for p40 in two adenomas. In two adenomas squamoid morules are focally positive for synaptophysin, and in one adenoma chromogranin was focally positive. In all nineteen adenomas squamoid morules were negative for Ki-67. Squamoid morules are characterized by strong male predominance, large adenoma size, beta-catenin nuclear positivity, CK5/6 expression, and no Ki-67 expression. Beta-catenin nuclear expression is helpful in distinguishing squamoid morules from foci of microinvasion and neuroendocrine differentiation.