Expression of Fascin-1 and its diagnostic value in liver cancer.

Although some studies have reported on the expression and clinical significance of Fascin-1 (FSCN1) in liver cancer, the clinical application and differential diagnosis value of FSCN1 in liver cancer are still unclear. The aim of this study was to analyze the expression level of FSCN1 protein in liver cancer tissues and explore its diagnostic and application value in differentiating between hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). The immunehistochemical analysis was used to detect the expression of FSCN1 in 108 cases of HCC, 26 cases of ICC, 23 cases of liver cirrhosis, and 11 cases of normal liver tissues. The differences in the positive expression rate and strong positive expression rate of FSCN1 among different groups were analyzed. The positive rate of FSCN1 in normal liver tissues, liver cirrhosis, HCC, and ICC tissues was 0.0% (0/11), 0.0% (0/23), 13.9% (15/108), and 92.3% (24/26), respectively, while the strong positive rate was 0.0% (0/11), 0.0% (0/23), 0.9% (1/108), and 69.2% (18/26), respectively. Both the positive rate and strong positive rate of FSCN1 in ICC tissues were significantly higher than those in HCC, liver cirrhosis, and normal liver tissues. Additionally, the positive rate of FSCN1 in moderately to poorly differentiated HCC tissues was 18.8% (15/80), significantly higher than in well-differentiated HCC (0.0%, 0/28) (P = 0.031). In liver cancer, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of FSCN1 positive prediction for ICC were 92.3%, 86.1%, 61.5%, and 97.9%, respectively, whereas the sensitivity, specificity, PPV, and NPV of FSCN1 strong positive prediction for ICC were 69.2%, 99.1%, 94.7%, and 93.0%, respectively. These results suggest that FSCN1 may play an important role in the occurrence and progression of liver cancer, and it can be used as a novel diagnostic marker for ICC.

Relevance and mechanism of STAT3/miR-221-3p/Fascin-1 axis in EGFR TKI resistance of triple-negative breast cancer.

The epidermal growth factor receptor 1 (EGFR) plays a crucial role in the progression of various malignant tumors and is considered a potential target for treating triple-negative breast cancer (TNBC). However, the effectiveness of representative tyrosine kinase inhibitors (TKIs) used in EGFR-targeted therapy is limited in TNBC patients. In our study, we observed that the TNBC cell lines MDA-MB-231 and MDA-MB-468 exhibited resistance to Gefitinib. Treatment with Gefitinib caused an upregulation of Fascin-1 (FSCN1) protein expression and a downregulation of miR-221-3p in these cell lines. However, sensitivity to Gefitinib was significantly improved in both cell lines with either inhibition of FSCN1 expression or overexpression of miR-221-3p. Our luciferase reporter assay confirmed that FSCN1 is a target of miR-221-3p. Moreover, Gefitinib treatment resulted in an upregulation of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in MDA-MB-231 cells. Using Stattic, a small-molecule inhibitor of STAT3, we observed a significant enhancement in the inhibitory effect of Gefitinib on the growth, migration, and invasion of MDA-MB-231 cells. Additionally, Stattic treatment upregulated miR-221-3p expression and downregulated FSCN1 mRNA and protein expression. A strong positive correlation was noted between the expression of STAT3 and FSCN1 in breast cancer tissues. Furthermore, patients with high expression levels of both STAT3 and FSCN1 had a worse prognosis. Our findings suggest that elevated FSCN1 expression is linked to primary resistance to EGFR TKIs in TNBC. Moreover, we propose that STAT3 regulates the expression of miR-221-3p/FSCN1 and therefore modulates resistance to EGFR TKI therapy in TNBC. Combining EGFR TKI therapy with inhibition of FSCN1 or STAT3 may offer a promising new therapeutic option for TNBC.

Infiltrative solid papillary carcinoma of the breast with axillary lymph node metastasis: a case report.

BACKGROUND: Solid papillary carcinoma (SPC) is a rare breast papillary tumor variant. The main histological features of SPC consist of neoplastic cell-rich nodules with thin fibrovascular cores, often accompanied by mucous secretion and neuroendocrine differentiation. Infiltrative solid papillary carcinoma (ISPC) tumor cells have an invasive, map-like growth pattern with serrated irregular growth. Due to its unique clinicopathological features, SPC is classified as two pathological tissue types based on the 2019 WHO classification of breast tumors: SPC in situ and ISPC. CASE PRESENTATION: We report a case of a 55-year-old female patient who was admitted to the hospital due to a painless left breast mass that had persisted for two years. Mammography suggested a mass in the left upper outer quadrant (BI-RADS 4B), and ultrasound of the breast demonstrated a cystic mass of the left breast (US_BI_RADS 4 C) with multiple enlarged lymph nodes in the left axilla. Postoperative pathology revealed ISPC with one lymph node metastasis in the left breast. Modified radical mastectomy was performed on the left breast. Subsequently, the patient received letrozole endocrine therapy, epirubicin hydrochloride and cyclophosphamide chemotherapy, and radiotherapy of the left chest wall and left upper and lower clavicular regions. After 17 months of follow-up, there was no evidence of recurrence or distant metastasis. CONCLUSIONS: SPC is a group of heterogeneous tumors. SPC in situ has a good prognosis. In contrast, ISPC has a unique histological morphology and growth pattern with invasive biological behavior that can lead to lymph node and distant metastases.

Case report: Superficial cervicovaginal myofibroblastoma of the cervix with endometrial carcinoma.

Introduction: A superficial cervical vaginal myofibroblastoma is a rare mesenchymal tumor, originating from the superficial stroma of the vagina and cervix. This study reports a patient, who was diagnosed with endometrioid carcinoma and a concomitant benign superficial cervicovaginal myofibroblastoma. Case presentation: A 53-year-old female with endometrial carcinoma was admitted to the Department of Gynecology of our hospital. She had a history of breast cancer on May 23, 2010, and took toremifene citrate for 41 months. Radical resection of the endometrial carcinoma was performed at our hospital. Based on the pathological findings, she was postoperatively diagnosed with endometrial adenocarcinoma with superficial cervical vaginal myofibroblastoma. The patient continued receiving postoperative breast cancer treatment. She underwent follow-up for 23 months. No recurrence or metastasis of the endometrial cancer or superficial cervical vaginal myofibroblastoma was observed. Conclusion: There were similarities between superficial cervical vaginal myofibroblastoma and other mesenchymal tumors of the female genital tract. Superficial cervical vaginal myofibroblastomas have a good prognosis, and the combination of tissue morphology and immunohistochemistry helped establish a definitive diagnosis.

Estrogen receptor α inhibits Caveolin 1 translation by promoting m6A-dependent miR199a-5p maturation to confer nab-paclitaxel resistance.

Estrogen receptor positive (ER+) breast cancer patients exhibit poorer responsiveness to nab-paclitaxel compared to ER negative (ER-) patients, with the underlying mechanisms remaining unknown. Caveolin 1 (CAV1) is a membrane invagination protein critical for the endocytosis of macromolecules including albumin-bound chemotherapeutic agents. Here, we demonstrate that ERα limits the efficacy of nab-paclitaxel in breast cancer cells while genetic or pharmacological inhibition of ERα increased the sensitivity of ER+ breast cancer cells to nab-paclitaxel. Notably, CAV1 expression inversely correlates with ERα and relates to improved clinical outcomes from nab-paclitaxel treatment. Importantly, ERα stimulates m6A dependent maturation of miR199a-5p, which is elevated in ER+ breast cancer, to inhibit CAV1 translation by antagonizing m6A modification of CAV1 mRNA. Together, our findings reveal a novel role of ERα in promoting m6A modification and subsequent maturation of miR199a-5p, which is upregulated in ER+ breast cancer, leading to the suppression of m6A modification of CAV1 and its mRNA translation, thereby contributing to nab-paclitaxel resistance. Thus, combining an ER antagonist with nab-paclitaxel could offer a promising strategy for treating ER+ breast cancer patients.

Case report: Hepatic epithelioid angiomyolipoma with elevated alpha-fetoprotein and a history of breast cancer.

Background: Perivascular epithelioid cell tumors have characteristic histological and immunohistochemical profiles. Epithelioid angiomyolipomas in the liver have particularly rare characteristics. These tumors are relatively small and lack clinical and imaging specificity. Thus, they can be easily misdiagnosed as other primary or metastatic tumors prior to surgery. Due to the significant epithelioid morphology and atypia of hepatic epithelioid angiomyolipoma (HEAML), intraoperative frozen section pathologic diagnosis might be challenging. Case presentation: A 33-year-old woman was admitted to our hospital for elevated alpha-fetoprotein (AFP) levels after a regular checkup following breast cancer surgery. Initially, liver cancer was suspected based on enhanced magnetic resonance imaging and color Doppler ultrasonography. Her serum AFP levels were 23.05 ng/ml. The patient underwent laparoscopic right hepatic tumor resection. Based on intraoperative cryopathology, hepatocellular carcinoma was considered a likely diagnosis. However, postoperative pathology confirmed a right HEAML. The patient underwent regular checkups for 23 months without exhibiting recurrence or distant metastasis. Conclusion: HEAML can be easily misdiagnosed on preoperative imaging and intraoperative cryopathology. Medical professionals must be aware of this possibility and proceed with caution. Postoperative pathological examination with assessment of IHC markers was helpful in diagnosing HEAML. HEAML has low malignant potential. Surgical resection is the mainstay of treatment, and most patients have a good prognosis.

The impact of Angiopoietin-2 genetic polymorphisms on susceptibility for malignant breast neoplasms.

Breast cancer causes morbidity and mortality among women worldwide, despite much research illuminating the genetic basis of this disease. Anti-angiogenesis therapies have been widely studied, although the association between angiopoietin-2 (ANGPT2) single nucleotide polymorphisms (SNPs) and breast cancer subtypes remains unclear. This case-control study included 464 patients with malignant breast neoplasms and 539 cancer-free females. We explored the effects of ANGPT2 SNPs on the susceptibility for a malignant breast neoplasm in a Chinese Han population. Five ANGPT2 SNPs (rs2442598, rs734701, rs1823375, 11,137,037, and rs12674822) were analyzed using TaqMan SNP genotyping. Carriers of the variant GG allele of rs1823375 were less likely than wild-type carriers to be diagnosed with clinically staged breast cancer, while females with human epidermal growth factor receptor 2 (HER2)-enriched disease carrying the CG or the CG+GG genotype at rs1823375 were significantly less likely than CC genotype carriers to be of lymph node status N1-N3. We also found that the T-T-C-A-T ANGPT2 haplotype significantly increased the risk for developing a malignant breast neoplasm by 1.385-fold (95% CI: 1.025-1.871; p < 0.05). Our study is the first to document a correlation between ANGPT2 polymorphisms and the development and progression of a malignant breast neoplasm in females of Chinese Han ethnicity.

Case Report: Hemangioblastoma- Like Clear Cell Stromal Tumor of the Left Lower Lung.

Background: Hemangioblastoma-like clear cell stromal tumor (HLCCST) is a recently reported neoplasm of the lung. Only 13 cases have been reported in four recent studies. Because HLCCST is very rare, it has not been included in the 2021 WHO classification of lung tumors. Case Presentation: We report a case of HLCCST of the left lower lung in a 40-year-old female who was admitted to our hospital after pulmonary nodules were discovered. A plain chest CT scan showed a nodular high-density shadow measuring approximately 8 mm in diameter in the left lower lung. The lesion had clear borders, uneven internal density, and a low-density central vacuolar area. The left lower lung was partially resected by video-assisted thoracic surgery. Post-operative histopathologic diagnosis "hemangioblastoma-like clear cell stromal tumor" of the left lower lung. Conclusion: The HLCCST is an extremely rare tumor and needs long-term follow-up after operation. Clinically, it may be easily confused with other benign and malignant tumors of the lung, and diagnosis is solely determined by histopathologic examination. This case suggests that immunohistochemical CD34 can be a strong positive marker.

Clinical and imaging findings of sarcomatoid renal cell carcinoma.

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Case Report: Benign Uterine Adenomyoma Metastasis in the Right Lung.

Background: Pulmonary metastasis of benign uterine leiomyoma and uterine endometriosis has been reported; however, pulmonary benign metastasizing uterine adenomyoma has not been reported. Herein, we report the first case of pulmonary benign metastasizing uterine adenomyoma. It is very important to differentiate from pulmonary primary synovial sarcoma; histopathology and immunohistochemistry are very helpful, molecular pathology can be used if necessary. Case Presentation: A female patient was admitted to the hospital because of pulmonary nodules. Lung computed tomography (CT) showed a nodular high density shadow in the upper lobe of the right lung, with a clear boundary and a diameter of approximately 1.2 cm. A contrast CT scan showed obvious enhancement, and no obvious lobulation or burr was found. Video-assisted thoracoscopic resection of the tumor was performed. The upper lobe nodules were completely removed. Postoperative pathological report confirmed the lesion as metastatic benign adenomyoma of the right upper lung. Conclusion: The lung is the most common organ for malignant tumor metastasis, and a few benign tumors can also develop pulmonary metastasis. Pulmonary benign metastasizing adenomyoma is extremely rare, and the prognosis is very good after surgical resection. When pulmonary CT shows a solid high-density shadow, we should consider the possibility of a metastatic benign tumor.

Upregulated WTAP expression in colorectal cancer correlates with tumor site and differentiation.

Few reports exist regarding the expression and function of Wilms' tumor 1-associated protein (WTAP) in colorectal cancer (CRC), and the evidence is controversial. Our analysis explored the expression of WTAP in CRC tissue, and analyzed its clinical and prognostic significance. WTAP expression was significantly higher in CRC tissue than in colorectal adenoma and normal colorectal tissue. WTAP was highest in left colon tumor samples and negatively associated with tumor differentiation, as well as depth of tumor invasion. In multiple logistic regression analysis, independent predictors of WTAP expression in CRC included tumor in the left colon (odds ratio = 2.634; 95% confidence interval: 1.129-6.142; P = 0.025) and poorly differentiated tissue (0.072; 0.014-0.367; P = 0.002). No clear relationship was observed between CRC patient prognosis and WTAP expression. We suggest that WTAP expression is upregulated in CRC, highly expressed in left colon cancer and negatively correlated with tumor differentiation.

Upregulated WTAP expression appears to both promote breast cancer growth and inhibit lymph node metastasis.

It is unclear as to whether Wilms' tumor 1-associated protein (WTAP) promotes or suppresses breast cancer. This immunohistochemistry analysis explored levels of WTAP expression in 347 cases of breast cancer and analyzed the relationship between WTAP expression and the clinicopathological characteristics and prognosis of breast cancer patients. The rate of high WTAP expression was significantly higher in breast cancer tissue than in adjacent normal breast tissue (37.5% vs 0.0%; P < 0.001). WTAP expression was positively associated with tumor size and grade, and negatively associated with axillary lymph node metastasis, estrogen and progesterone receptor status. Rates of high WTAP expression were 66.1% in triple-negative breast cancer (TNBC) tissue and 31.3% in non-TNBC tissue. In multiple logistic regression analysis, independent predictors of WTAP expression in breast cancer included larger tumor size (odds ratio = 1.907; 95% confidence interval: 1.185-3.067; P = 0.008), lymph node metastasis (0.597; 0.373-0.956; P = 0.032) and TNBC status (3.735; 2.056-6.784; P < 0.001). No clear relationship was observed between patient prognosis and WTAP expression. We suggest that WTAP expression is upregulated in breast cancer and appears to both promote tumor growth and inhibit lymph node metastasis.

Combined High Resistin and EGFR Expression Predicts a Poor Prognosis in Breast Cancer.

Elevated levels of resistin and epidermal growth factor receptor (EGFR) facilitate the development of breast cancer, although there are no reports of any correlation between these proteins. This study analyzed 392 human breast cancer tissue specimens and 42 samples of adjacent normal tissue. Rates of positive and strongly positive resistin expression were significantly higher in breast cancer tissue than in the adjacent nontumor tissue (83.2% vs. 23.8% and 20.9% vs. 0.0%, respectively; P < 0.001 for both comparisons). Positive resistin expression was significantly associated with tumor size, grade, stage, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status, and molecular classification; strongly positive resistin expression was associated with tumor grade, ER, PR, HER2 status, and molecular classification. Significantly positive correlations were observed between positive and strongly positive resistin expression and corresponding levels of EGFR expression. Relapse-free and overall survival was worse for patients with high levels of both proteins than for those with high levels of only one protein or normal levels of both proteins. Our evidence suggests that combined high levels of resistin and EGFR expression correlate with survival in patients with breast cancer.

Downregulated METTL14 Expression Correlates with Breast Cancer Tumor Grade and Molecular Classification.

It is unclear whether the methyltransferase-like 14 (METTL14) protein promotes or suppresses cancer growth. We examined the association between METTL14 expression, cancer progression, and patient prognosis in a total of 398 breast cancer tissue specimens. Significantly fewer cancer tissue specimens compared with normal breast tissue expressed high levels of METTL14 (52.8% vs. 75.0%). METTL14 expression was negatively associated with tumor grade and positively associated with patient age, estrogen, and progesterone receptor status. High METTL14 expression was more common in luminal A and luminal B tissue (75.9% and 60.8%, respectively), compared with human epidermal growth factor receptor 2- (HER2-) enriched and triple-negative breast cancer (TNBC) samples (38.2% and 18.6%, respectively). In multiple logistic regression analysis, independent predictors of METTL14 expression in breast cancer included higher tumor grade (odds ratio (OR) = 0.494, 95% confidence interval (CI): 0.289-0.844; P = 0.010), TNBC subtype (OR = 0.109, 95% CI: 0.054-0.222; P < 0.001), and HER2-enriched subtype (OR = 0.298, 95% CI: 0.156-0.567; P < 0.001). No clear relationship was observed between patient prognosis and METTL14 expression. It appears that downregulated METTL14 expression in breast cancer is associated with tumor grade and molecular classification.

Subcellular localization of HMGB1 in colorectal cancer impacts on tumor grade and survival prognosis.

The high-mobility group box-1 (HMGB1) protein is implicated in the development of various cancers and their proliferation. According to its function, HMGB1 shuttles between the cell nucleus and cytoplasm, assisting with nucleosome stabilization and gene transcription, or localizing in the cell membrane for outgrowth. The clinicopathologic and prognostic significance of these different subcellular locations and their correlation has been unclear in colorectal cancer (CRC). We found significantly higher rates of nuclear HMGB1 expression in CRC and colorectal adenoma tissue samples (84.0% and 92.6%, respectively) than in normal colorectal tissue (15.0%) and a significantly higher rate of positive cytoplasmic HMGB1 expression in CRC tissue (25.2%) compared with colorectal adenoma (11.8%) and normal colorectal tissue (0.0%). Positive cytoplasmic HMGB1 expression was associated with high-grade CRC, a poor prognosis, and was negatively correlated with strongly positive nuclear HMGB1 expression in CRC tissue specimens (r = - 0.377, P = 0.000). CRC patients with strongly positive nuclear HMGB1 expression had a better survival prognosis than other CRC patients. Preventing nuclear plasma translocation of HMGB1 may be a new strategy for CRC management.