bromochloroacetic-acid and Esophageal-Squamous-Cell-Carcinoma

While most resection specimens from patients with neoadjuvantly treated esophageal squamous cell carcinoma show therapy-related changes in the form of inflammation and fibrosis, others harbor a florid foreign body-type giant cell response to keratin debris. The purpose of our study was to perform a detailed clinicopathologic analysis of these histologic types of treatment responses and correlate these findings with patient outcome. Clinical and pathologic parameters from 110 esophagogastrectomies were recorded and analyzed. Two main types of histologic responses were observed: inflammatory-predominant response (59%) and florid foreign body-type giant cell response to keratin (41%). Irrespective of cG, cTNM, and amount of residual cancer, florid foreign body-type giant cell reaction was predominantly noted deep within the esophageal wall, while the inflammatory response was restricted to the mucosa, submucosa, and inner half of muscularis propria. Patients with foreign body-type giant cell response showed significantly better overall survival compared with the inflammatory response group (log-rank test P=0.015). Florid foreign body-type giant cell response was the only factor associated with improved survival in a multivariable analysis for overall survival (hazard ratio=0.5; 95% confidence interval=0.3-1.0; P=0.038), but not in the model for disease-specific survival, whereas ypTNM stage II was the only significant risk factor for disease-specific survival in multivariable analysis (hazard ratio=3.4; 95% confidence interval=1.0-11.2; P=0.047). Our results suggest that in addition to the College of American Pathologists Tumor Regression Score and ypTNM stage, subtype of histologic response to therapy may represent another prognostic marker for neoadjuvantly treated esophageal squamous cell carcinoma.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Chemotherapy, Adjuvant; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Esophagectomy; Female; Gastrectomy; Granuloma, Foreign-Body; Humans; Keratins; Male; Middle Aged; Neoadjuvant Therapy; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome

Topics: Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Esophagoscopy; Humans; Keratins; Squamous Cell Carcinoma of Head and Neck

Tumor budding is known predictors of lymph node metastasis from esophageal squamous cell carcinoma. However, it is not easy to detect such small cell clusters on hematoxylin-eosin (HE) staining. Therefore, we evaluated tumor budding using immunohistochemistry (IHC) for epithelial cell markers.. We analyzed tumor budding in 50 cases of superficial esophageal squamous cell carcinoma. We evaluated the impact of clinicopathological factors and tumor budding to predict lymph node metastasis. A total of 565 tumor sections were assessed using HE staining and IHC for cytokeratin 5/6.. Based on receiver operating characteristic curves, the cut-off values for high-grade tumor budding evaluated using HE staining or IHC were 2 and 11, respectively. High-grade tumor budding evaluated using HE staining (P = 0.007) and IHC (P ≤ 0.001) were significantly correlated with lymph node metastasis. For tumors with pT1a-MM to pT1b-SM1, high-grade tumor budding evaluated using IHC was correlated with lymph node metastasis (P = 0.050).. Tumor budding was significantly associated with lymph node metastasis. The optimal cut-off values of tumor budding on HE staining and tumor budding on IHC were 2 and 11, respectively. Even though both tumor budding on HE staining and tumor budding on IHC were significantly associated with lymph node metastasis, tumor budding on IHC tend to be more associated with lymph node metastasis.

Topics: Aged; Aged, 80 and over; Epithelial Cells; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Female; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Grading; Predictive Value of Tests; Retrospective Studies; ROC Curve; Staining and Labeling; Tumor Burden

Esophageal cancer is a common human malignant tumor with high mortality. Glandular epithelial markers, such as CAM5.2, can be expressed in esophageal squamous cell carcinoma (ESCC), but the clinical significance of these cells in ESCC remains elusive.Immunohistochemical analysis of CAM5.2 was performed on 604 ESCC specimens using tissue microarray. Our study design and study population used retrospective cohorts based on the hospital information system and pathological information management system which included medical information, date of admission, procedures undergone, registration, examinations, and medication.In total, positive staining of CAM5.2 was 145 of 604 (24%). Statistical analysis showed that the expression of CAM5.2 had no relationship with sex, age, tumor differentiation, tumor size, tumor-node-metastasis (TNM) classification, and lymph node metastasis, but it was significantly associated with poor prognosis of overall survival (P = .0041) and disease-free survival (P = .0048) in ESCC patients.Herein, we report for the first time that the high expression of the CAM 5.2 is an independent predictor of poor prognosis in patients with ESCC.

Topics: Adult; Aged; Biomarkers; Biopsy; China; Cohort Studies; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Prognosis; Retrospective Studies; Transcriptome

Circulating tumor cells (CTCs) are tumor cells present in the bloodstream, which originate from tumor sites, and are ultimately responsible for metastasis or relapse in several types of cancer. However, to the best of our knowledge, only a few studies have investigated these extremely rare cells in esophageal squamous cell carcinoma (ESCC). In the present study, 63 patients with ESCC and 50 healthy donors were recruited, and the potential clinical significance of CTCs was assessed using subtraction enrichment and immunostaining‑fluorescence in situ hybridization. Blood samples were collected at the following times: At first diagnosis, following neoadjuvant chemoradiotherapy, 24 h and 13 days post‑surgery, and every 3 months during follow‑up. Cytokeratin (CK)‑positive and clustered CTCs only accounted for 1% of total CTCs detected, whereas most CTCs were CK‑negative aneuploid cells. Patients with ESCC (n=63) had higher CTC counts compared with healthy donors (control group; n=50) (area under curve=0.807, median CTC count, 2 vs. 0). However, there was no statistical association between CTC counts and sex, age, pathological stage, tumor location, tumor depth or lymph node involvement (P>0.05). The association of tumor development with CTC status and other circulating biomarkers was monitored in patients for a further 2 years. The results revealed that a change in CTC counts between first diagnosis and 13 days post‑surgery (ΔCTC) of ≥2/7.5 ml peripheral blood could be applied for predicting progression‑free survival (hazard ratio, 3.922; 95% confidence interval, 0.907‑16.951; P<0.05) in patients with ESCC. In conclusion, ΔCTC evaluation may be a promising indicator for predicting tumor prognosis and the clinical efficacy of treatment in patients with ESCC.

Topics: Adult; Aged; Biomarkers, Tumor; Case-Control Studies; Cell Count; Chemoradiotherapy, Adjuvant; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Female; Humans; In Situ Hybridization, Fluorescence; Keratins; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Grading; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplastic Cells, Circulating; Progression-Free Survival

Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy with a poor prognosis due to its highly invasive and metastatic potential. The molecular pathogenesis underlying the invasive mechanism of ESCC is not well known because of the lack of existing models to study this disease. p120-Catenin (p120ctn) and the epidermal growth factor receptor (EGFR) have each been implicated in several cancers, including ESCC. p120ctn is down-regulated in 60% of ESCC tumors, whereas EGFR is the most commonly overexpressed oncogene in ESCC. For these reasons, we investigated the cooperation between p120ctn and EGFR and its effect on ESCC invasion. We show that p120ctn down-regulation is commonly associated with EGFR overexpression. By using a three-dimensional culture system, we demonstrate that the inverse relationship between p120ctn and EGFR has biological implications. Specifically, p120ctn down-regulation coupled with EGFR overexpression in human esophageal keratinocytes (EPC1-PE) was required to promote invasion. Morphological comparison of EPC1-PE cells grown in three-dimensional culture and human ESCC revealed identical features, including significantly increased cellularity, nuclear grade, and proliferation. Molecular characteristics were measured by keratin expression patterns, which were nearly identical between EPC1-PE cells in three-dimensional culture and ESCC samples. Altogether, our analyses have demonstrated that p120ctn down-regulation and EGFR overexpression are able to mimic human ESCC in a relevant three-dimensional culture model.

Topics: Antigens, CD; Cadherins; Carcinoma, Squamous Cell; Catenins; Cell Culture Techniques; Cell Line, Tumor; Cell Movement; Delta Catenin; Down-Regulation; Epithelium; ErbB Receptors; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Keratins; Neoplasm Invasiveness

Undifferentiated carcinoma of the esophagus is a rare histologic variant of esophageal carcinoma. Using criteria based on studies of undifferentiated carcinomas arising at other sites, we have collected 16 cases of resected esophageal undifferentiated carcinomas. Patients ranged in age from 39 to 84 years (mean, 65.5 years) and were predominantly male (94%). The tumors were characterized by an expansile growth pattern of neoplastic cells organized in solid sheets and without significant glandular, squamous, or neuroendocrine differentiation. The neoplastic cells had a syncytial-like appearance, little intervening stroma, and patchy tumor necrosis. In a subset of cases, the tumor cells adopted a sarcomatoid (n = 2), rhabdoid (n = 1), or minor component (<5%) of glandular morphology (n = 3). In 1 case, reactive osteoclast-like giant cells were found interspersed among the neoplastic cells. Lymphovascular invasion, perineural invasion, and lymph node metastases were identified in 88%, 56%, and 81% of cases, respectively. In 12 (75%) specimens, the background esophageal mucosa was notable for Barrett esophagus. Consistent with the epithelial nature of these neoplasms, cytokeratin positivity was identified in all cases. In addition, SALL4 expression was present in 8 (67%) of 12 cases. Follow-up information was available for 15 (94%) of 16 patients, all of whom were deceased. Survival after surgery ranged from 1 to 50 months (mean, 11.9 months). Before death, 67% patients had documented locoregional recurrence and/or distant organ metastases. In summary, esophageal undifferentiated carcinomas are aggressive neoplasms and associated with a high incidence of recurrence and/or metastases and a dismal prognosis.

Topics: Adult; Aged; Aged, 80 and over; Alcohol Drinking; Anemia; Barrett Esophagus; Biomarkers, Tumor; Carcinoma; Carcinoma, Squamous Cell; Comorbidity; Deglutition Disorders; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Female; Follow-Up Studies; Gastroesophageal Reflux; Humans; Immunohistochemistry; In Situ Hybridization; Keratins; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplasms, Second Primary; Prognosis; Smoking; Survival Rate; Transcription Factors; Treatment Outcome

To investigate the reasons for the occurrence of the pink-color sign of iodine-unstained lesions.. In chromoendoscopy, the pink-color sign of iodine-unstained lesions is recognized as useful for the diagnosis of esophageal squamous cell carcinoma. Patients with superficial esophageal neoplasms treated by endoscopic resection were included in the study. Areas of mucosa with and without the pink-color sign were evaluated histologically. The following histologic features that were possibly associated with the pink-color sign were evaluated. The keratinous layer and basal cell layer were classified as present or absent. Cellular atypia was classified as high grade, moderate grade or low grade, based on nuclear irregularity, mitotic figures, loss of polarity, chromatin pattern and nuclear/cytoplasmic ratio. Vascular change was assessed based on dilatation, tortuosity, caliber change and variability in shape. Vessels with these four findings were classified as positive for vascular change. Endoscopic images of the lesions were captured immediately after iodine staining, 2-3 min after iodine staining and after complete fading of iodine staining. Quantitative analysis of color changes after iodine staining was also performed.. A total of 61 superficial esophageal neoplasms in 54 patients were included in the study. The lesions were located in the cervical esophagus in one case, the upper thoracic esophagus in 10 cases, the mid-thoracic esophagus in 33 cases, and the lower thoracic esophagus in 17 cases. The median diameter of the lesions was 20 mm (range: 2-74 mm). Of the 61 lesions, 28 were classified as pink-color sign positive and 33 as pink-color sign negative. The histologic diagnosis was high-grade intraepithelial neoplasia (HGIN) or cancer invading into the lamina propria in 26 of the 28 pink-color sign positive lesions. There was a significant association between pink-color sign positive epithelium and HGIN or invasive cancer (P = 0.0001). Univariate analyses found that absence of the keratinous layer and cellular atypia were significantly associated with the pink-color sign. After Bonferroni correction, there were no significant associations between the pink-color sign and presence of the basal membrane or vascular change. Multivariate analyses found that only absence of the keratinous layer was independently associated with the pink-color sign (OR = 58.8, 95%CI: 5.5-632). Quantitative analysis was performed on 10 superficial esophageal neoplasms with both pink-color sign positive and negative areas in 10 patients. Pink-color sign positive mucosa had a lower mean color value in the late phase (pinkish color) than in the early phase (yellowish color), and had similar mean color values in the late and final phases. These findings suggest that pink-color positive mucosa underwent color fading from the color of the iodine (yellow) to the color of the mucosa (pink) within 2-3 min after iodine staining. Pink-color sign negative mucosa had similar mean color values in the late and early phases (yellowish color), and had a lower mean color value in the final phase (pinkish color) than in the late phase. These findings suggest that pink-color sign negative mucosa did not undergo color fading during the 2-3 min after iodine staining, and underwent color fading only after spraying of sodium thiosulfate.. The pink-color sign was associated with absence of the keratinous layer. This sign may be caused by early fading of iodine staining.

Topics: Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Cell Nucleus; Color; Cytoplasm; Duodenoscopy; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Esophagoscopy; Female; Humans; Iodine; Keratins; Male; Middle Aged; Mitosis; Mucous Membrane; Staining and Labeling; Time Factors