ABSTRACT
BACKGROUND: Hematological recurrence is the second most frequent cause of failure in the treatment of gastric cancer. The detection of circulating tumor markers in peripheral blood by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) method may be a useful tool to predict recurrence and determine the patient's prognosis. However, no consensus has been reached regarding the association between the tumor markers level in peripheral blood and its impact on patient survival. AIMS: To evaluate the expression of the circulating tumor markers CK20 and MUC1 in peripheral blood samples from patients with gastric cancer by qRT-PCR, and to verify the association of their expression levels with clinicopathological characteristics and survival. METHODS: A total of 31 patients with gastric adenocarcinoma were prospectively included in this study. CK20 and MUC1 expression levels were analyzed from peripheral blood by the qRT-PCR technique. RESULTS: There was no statistically significant (p>0.05) association between CK20 expression levels and clinical, pathological, and surgical features. Higher MUC1 expression levels were associated with female patients (p=0.01). There was a correlation between both gene levels (R=0.81, p<0.001), and CK20 level and tumor size (R=0.39, p=0.034). CONCLUSIONS: CK20 and MUC1 expression levels could be assessed by qRT-PCR from total peripheral blood samples of patients with gastric cancer. CK20 levels were correlated to MUC1 levels as well as to tumor size. There was no difference in disease-free survival and overall survival regarding both genetic markers expression in this series.
Subject(s)
Neoplastic Cells, Circulating , Stomach Neoplasms , Humans , Female , Reverse Transcriptase Polymerase Chain Reaction , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , Neoplastic Cells, Circulating/pathology , Keratin-20/genetics , Keratin-20/metabolism , Biomarkers, Tumor/geneticsABSTRACT
BACKGROUND: The incidence of adenocarcinoma of the ampulla of Vater has been increasing over the past years. Nevertheless, it is still a rare disease and the prognostic factors predicting long-term survival are not sufficiently clarified. This study aims to evaluate the association between histopathological characteristics and long-term survival of patients with ampullary cancer after curative resection, as well as the efficiency of immunohistochemical expression of CK7, CK20, and CDX2 to distinguish the histopathological (intestinal or pancreaticobiliary) patterns. METHODS: Demographic, histopathological data, pTNM stage, and immunohistochemical expression patterns were collected from 65 patients with adenocarcinoma of the ampulla of Vater. Five and 10-year overall and disease-free survival rates after curative resection were determined. RESULTS: Of the 65 patients with ampullary carcinoma, 47 (72%) underwent radical resection. The 5- and 10-year overall survival rate was 46% and 37%, respectively. Our results demonstrate that the main prognostic factors were the presence and number of lymph node metastases, lymph node ratio (LNR), differentiation grade, and lymphovascular invasion. After multivariate analysis, only lymph node ratio ≥ 20% remained an independent prognostic factor of survival (HR: 2.63 95% CI: 1.05-6.61; p = 0.039). CONCLUSION: Here, we demonstrated more evidence that the lymph node metastases are associated with poor prognosis in ampullary carcinoma. Particularly, the relation between the number of metastatic lymph nodes and the number of harvested lymph node (LNR) should be considered a major prognostic factor.
Subject(s)
Adenocarcinoma/epidemiology , Adenocarcinoma/pathology , Ampulla of Vater/pathology , Common Bile Duct Neoplasms/epidemiology , Common Bile Duct Neoplasms/pathology , Adenocarcinoma/surgery , Adult , Aged , Aged, 80 and over , Ampulla of Vater/surgery , Biomarkers, Tumor , Brazil , CDX2 Transcription Factor , Common Bile Duct Neoplasms/surgery , Databases, Factual , Disease-Free Survival , Female , Humans , Immunohistochemistry , Keratin-20 , Lymphatic Metastasis/pathology , Male , Middle Aged , Prognosis , Survival Rate , Young AdultABSTRACT
OBJECTIVE: To determine if individual, instead of group, patient progression risk could be predicted using p53, Ki67 and CK20 biomarker percentage values at initial transurethral resection of bladder tumor specimens. METHODS: This was an observational study where biomarkers were measured with no knowledge of tumor outcome. Initial bladder tumor specimens were classified as non-invasive and invasive to sub-epithelium (pT1). Percentages of stained biomarker cells were tested as progression predictors from non-invasive to pT1 and pT1 to pT2. Progression probability was correlated with biomarker percentages resulting in a regression equation. RESULTS: We studied 112 patients (median age = 67, range 37-91, males 83/112 (73%), with median follow-up of 39 months (range 1.7-140). Mean biomarker values were higher in stage pT1 than in non-invasive (all p < 0.001). Cut-off points separating progression from non-progression groups in stage pT1 were higher than in non-invasive for all biomarkers. Correlation R values for progression probability vs. biomarker percentages varied from 0.7 to 0.9 (all p < 0.001), regression slopes from 0.1 to 0.8 and intercepts from 11 to 35. A novel individual progression probability was calculated as the product of biomarker percentage of stained cells and slope, plus the prevalence-adjusted intercept. CONCLUSIONS: Identification of individual risk of progression in patients with non-muscle-invasive bladder tumors was possible using p53- and Ki67-derived progression probability using a regression equation. Combining biomarker-derived progression probability to tumor stage pT1 improves progression to pT2 predictive accuracy.
Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma, Papillary/metabolism , Urinary Bladder Neoplasms/metabolism , Adult , Aged , Aged, 80 and over , Carcinoma, Papillary/pathology , Carcinoma, Papillary/surgery , Disease Progression , Female , Humans , Keratin-20/metabolism , Ki-67 Antigen/metabolism , Male , Middle Aged , Neoplasm Staging , Predictive Value of Tests , Tumor Suppressor Protein p53/metabolism , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/surgeryABSTRACT
Malignant mesothelioma is an uncommon neoplasm that should be distinguished from the more common pulmonary adenocarcinomas and other metastatic lesions. Although diagnosis is based on morphologic features, immunohistochemical stains such as Calretinin, WT-1, CK-5/6, D2-40, Ber-Ep4, and MOC-31 are routinely used. Other organ-specific immunohistochemical markers are used when metastases from unknown primary lesion is suspected clinically. Here, we report a case of pleural epithelioid malignant mesothelioma expressing CK20. A 68-year-old male presented to the Emergency Department with nonproductive cough and progressive shortness of breath. Chest x-ray showed a large left-sided pleural effusion. Metastasis from a gastrointestinal primary was clinically suspected. Cytopathologic examination of the pleural fluid demonstrated atypical cells singly and in clusters with round nuclei, prominent nucleoli, and dense cytoplasm. The cell block demonstrated single and clusters of atypical cells positive for calretinin, D2-40, WT-1, CK-5/6, and CK7. Ber-EP4, MOC-31, TTF-1, Napsin-A, and CDX-2 were negative. CK20 was diffusely positive. A diagnosis of atypical mesothelial proliferation with aberrant CK20 expression was made. A subsequent pleural biopsy demonstrated sheets of highly atypical cells that were diffusely and strongly positive for the mesothelial markers and CK20. Multiple studies have shown malignant mesotheliomas to lack CK20 reactivity. To our knowledge, this is the first case report of a diffuse and strong CK20-positive mesothelioma. Such aberrant expressions should be kept in mind when cases are histologically atypical or lack reactivity for multiple mesothelial markers, especially when a gastrointestinal primary malignancy is suspected.
Subject(s)
Adenocarcinoma/diagnosis , Biomarkers, Tumor/metabolism , Keratin-20/metabolism , Lung Neoplasms/diagnosis , Mesothelioma/diagnosis , Pleural Effusion/diagnosis , Pleural Neoplasms/diagnosis , Aged , Diagnosis, Differential , Humans , Immunohistochemistry , Male , Mesothelioma, MalignantABSTRACT
Introducción: El carcinoma de células de Merkel (MCC) es un tumor cutáneo maligno agresivo y de mal pronóstico. La incidencia es mayor en adultos hombres, caucásicos, con edad promedio de 70 años. Feng et al, lograron aislar un nuevo virus en muestras de este tumor, que denominaron virus polioma de células de Merkel (MCPyV). Se ha intentado establecer una relación causal entre el virus y MCC. El virus está integrado al genoma y produciría mutaciones específicas. En muestras de MCC, se ha detectado expresión de oncoproteinas virales (antígenos T) que promueven la replicación viral y tumorogénesis
Introduction: Merkel cell carcinoma (MCC) is an aggressive malignant cutaneous tumor with poor prognosis. Most cases affect elder patient with an average of 70 years of age. Feng et al isolated a new virus, the Merkel cell carcinoma polyoma virus (MCPyV). A causal relationship between MCPyV y MCC has been established. The virus is integrated in the genome and pro-duces specific mutations. MCC samples show ex-pression of viral oncoproteins (T antigens) that promote viral replication and tumorogenesis.
Subject(s)
Humans , Male , Female , Middle Aged , Aged , Skin Neoplasms/pathology , Skin Neoplasms/virology , Carcinoma, Merkel Cell/pathology , Carcinoma, Merkel Cell/virology , Polyomavirus Infections/complications , Prognosis , Skin Neoplasms/metabolism , Immunohistochemistry , Carcinoma, Merkel Cell/metabolism , Keratin-20/metabolismABSTRACT
BACKGROUND: The immunoreactivity of thyroid transcription factor-1 (TTF-1) is a very specific marker for lung and thyroid neoplasms; the expression of TTF-1 has also been demonstrated in extrapulmonary carcinomas. We examined the expression of TTF-1 in 15 intestinal-type adenocarcinomas of the extrahepatic bile duct. We then compared the expression to TTF-1 staining with other immunohistochemical markers including cytokeratin (CK) 7, CK20, caudal-type homeobox transcription factor 2 (CDX2), Napsin A, and MUC2. We additionally compared the clinicopathological prognostic factors with the TTF-1 expression status. RESULTS: Nuclear TTF-1 staining was detected in 2 cases (13.3%), and Napsin A was positive in the same 2 cases (13.3%). All cases were positive for CK20, CDX2, and MUC2; 5 cases were positive for CK7. There was no correlation between TTF-1 expression and the clinicopathological characteristics. CONCLUSIONS: To avoid potential pitfalls, TTF-1 should be interpreted in conjunction with the clinical setting, histology, and the results of markers such as CK7, CK20, Napsin A, and CDX2. This report is the first of TTF-1 positivity in adenocarcinomas from the extrahepatic biliary tract.
Subject(s)
Adenocarcinoma/metabolism , Bile Duct Neoplasms/metabolism , Nuclear Proteins/metabolism , Transcription Factors/metabolism , Adenocarcinoma/pathology , Adult , Aged , Aspartic Acid Endopeptidases/metabolism , Bile Duct Neoplasms/pathology , Biomarkers, Tumor/metabolism , CDX2 Transcription Factor , Homeodomain Proteins/metabolism , Humans , Keratin-20/metabolism , Keratin-7/metabolism , Male , Mucin-2/metabolism , Thyroid Nuclear Factor 1ABSTRACT
INTRODUCTION: Heat-induced epitope retrieval (HIER) of formalin-fixed paraffin-embedded tissues is now a standard practice in immunohistochemistry (IHC). In this study, we aimed to test the effect of altering HIER temperature on IHC staining quality at high altitude, the hypothesis being that lower HIER temperatures would result in improved staining patterns. MATERIALS AND METHODS: In a laboratory at high altitude (Aurora, CO), we used a platform with automated onboard epitope retrieval, and systematically tested 3 different HIER temperatures (100°C, 95°C, 90°C) with 4 IHC stains that are commonly used in routine practice: CD3, Ki67, CK20, and Melan A (n=10 for each antibody/epitope retrieval temperature combination). A scoring system was devised, the slides were scored in a blinded manner, and statistical analysis was performed. For comparison, the same study was performed in a laboratory near sea level (Atlanta, GA). RESULTS: At high altitude, lower HIER temperatures resulted in improved staining patterns, as quantified by stronger staining intensity and greater area of the slides stained. The scores obtained with HIER temperatures of 95°C and 90°C were higher than those obtained with HIER of 100°C, and the difference was found to be statistically significantly for some antibody/epitope retrieval temperature combinations (P<0.05). This effect was not seen in the laboratory near sea level. CONCLUSIONS: We show that alternate epitope retrieval recommendations are warranted for laboratories at high altitude. Furthermore, we suggest that manufactures should consider how their instruments will perform at high altitude as they further automate the process of IHC.
Subject(s)
Altitude , CD3 Complex , Hot Temperature , Immunohistochemistry/methods , CD3 Complex/chemistry , Humans , Immunohistochemistry/standards , Keratin-20/chemistry , Ki-67 Antigen/chemistry , MART-1 Antigen/chemistry , Paraffin Embedding , Quality ControlABSTRACT
Herein, correlations between expression levels of CK20 and efficacy of treatment and postoperative prognosis of colorectal cancer were evaluated to elucidate the clinical value of CK20. Postoperative follow-up was performed on 62 patients who underwent surgery for colorectal cancer between January 2010 and December 2010. Samples of tumor tissues and intraperitoneal drainage fluids were collected. Blood samples were obtained during the 2-year follow-up period. The expression of CK20 in surgical specimen, intraperitoneal drainage fluids, and postoperative serum samples was quantified by enzyme-linked immunosorbent assay, RT-PCR, and western blotting. Correlation between the levels of CK20 and postoperative outcomes was investigated by Spearman correlation analysis. In both tumor specimens and intraperitoneal drainage fluids, CK20 levels were lower in patients with earlier cancer stages than in those at later stages. During postoperative follow-up, serum negative CK20 patients had significantly higher 3-year survival rates than serum positive CK20 patients. All differences were statistically significant (P < 0.05). CK20 levels can provide clinically valuable information on the postoperative prognosis of patients with colorectal cancer.
Subject(s)
Biomarkers, Tumor/blood , Colorectal Neoplasms/blood , Colorectal Neoplasms/genetics , Aged , Colorectal Neoplasms/pathology , Colorectal Neoplasms/surgery , Female , Gene Expression Regulation, Neoplastic , Humans , Keratin-20/blood , Lymph Nodes/pathology , Male , Middle Aged , Neoplasm Staging , Postoperative Period , Prognosis , Survival RateABSTRACT
Primary mucinous adenocarcinomas of the ovary are a diagnostic challenge because their histologic and immunohistochemical features usually overlap with metastatic tumors. SATB2 is a recently identified protein with restricted expression in the glandular cells lining the lower gastrointestinal tract. The aim of this study is to examine the differential expression of SATB2 in primary and metastatic tumors of the ovary. Mucinous ovarian tumors of intestinal type were retrieved from the pathology files of the Instituto Nacional de Cancerología de México. A double reading of the hematoxylin and eosin-stained slides was performed to confirm the diagnosis, and a detailed review of the clinical chart was performed to define the primary origin of the tumor (ovarian vs metastatic). Immunohistochemical staining for CK20, CDX2, and SATB2 was performed and evaluated by 2 gynecopathologists. A total of 106 mucinous tumors were identified, 26 of which were considered to be metastatic, and 80 of which were primary ovarian tumors. All of the primary tumors that were not associated with cystic teratomas were negative for SATB2, and the 4 that were associated with a teratoma were positive for SATB2. All 20 of the metastatic tumors of the colon and appendix were positive for CK20, and 4 were positive for CK7. In addition, all 20 of these tumors were positive for SATB2, and 19 were positive for CDX2. SATB2 appears to be a useful marker for the diagnosis of primary vs metastatic mucinous intestinal-type neoplasms and is highly sensitive in detecting lower gastrointestinal tract metastasis.
Subject(s)
Adenocarcinoma, Mucinous/diagnosis , Biomarkers, Tumor/metabolism , Colonic Neoplasms/diagnosis , Colonic Neoplasms/pathology , Matrix Attachment Region Binding Proteins/metabolism , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/secondary , Transcription Factors/metabolism , Adenocarcinoma, Mucinous/metabolism , Adenocarcinoma, Mucinous/pathology , Adult , Aged , CDX2 Transcription Factor , Colonic Neoplasms/metabolism , Diagnosis, Differential , Female , Homeodomain Proteins/metabolism , Humans , Immunohistochemistry , Keratin-20/metabolism , Middle Aged , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Teratoma/pathologyABSTRACT
Reduced CDX2 and cytokeratin 20 (CK20) expression in colorectal carcinoma with BRAF mutation and high-level microsatellite instability (MSI-H) has been well documented. The immunophenotype of BRAF-mutated microsatellite stable (MSS) colorectal carcinoma has not been reported. We analyzed 205 colorectal carcinomas including 28 BRAF-mutated MSS, 53 BRAF-mutated MSI-H, and 124 BRAF wild-type MSS tumors for CDX2, cytokeratin 7 (CK7), and CK20 immunohistochemical expression. CDX2 was scored semiquantitatively for both staining intensity and percent of tumor cells staining and a modified CDX2 H-score was calculated. Patients with BRAF-mutated MSS colorectal carcinomas were more frequently stage IV at presentation compared to patients with BRAF-mutated MSI-H colorectal carcinomas and BRAF wild-type MSS colorectal carcinomas (32% versus 8% versus 15%, P < .001). BRAF-mutated MSS colorectal carcinoma displayed reduced CDX2 expression compared to BRAF wild-type MSS colorectal carcinoma (75% versus 94%; mean CDX2 H-score 98 versus 150, P < .001). CK7 expression was more often identified in BRAF-mutated MSS colorectal carcinoma compared to both BRAF-mutated MSI-H colorectal carcinoma and BRAF wild-type MSS colorectal carcinoma (39% versus 6% versus 6%, P = .0001). BRAF-mutated MSI-H colorectal carcinomas were less often CK20 positive compared to BRAF-mutated MSS and BRAF wild-type MSS tumors (70% versus 93% versus 90%, P = 0.001). In summary, BRAF-mutated MSS colorectal carcinoma often displays reduced CDX2 and increased CK7 expression. Knowledge of this altered immunophenotype is important as patients with BRAF-mutated MSS colorectal carcinoma often present with metastatic disease and the altered tumor immunophenotype may lead to the erroneous assumption that origin from the colon/rectum is unlikely.
Subject(s)
Adenocarcinoma/metabolism , Colorectal Neoplasms/metabolism , Homeodomain Proteins/metabolism , Keratin-7/metabolism , Proto-Oncogene Proteins B-raf/metabolism , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , CDX2 Transcription Factor , Colorectal Neoplasms/pathology , Female , Humans , Immunohistochemistry , Keratin-20/metabolism , Male , Microsatellite Instability , Microsatellite Repeats , Middle Aged , Mutation , PrognosisABSTRACT
Merkel cell carcinoma (MCC) is recognized by its morphologic features and by its classic immunophenotypic properties. Although MCCs demonstrating nonclassic immunoreactivities have been described, a case documenting a change in immunophenotype during the course of disease progression has not been previously reported. We report a case of MCC that initially demonstrated cytokeratin 20 positivity but lost expression in subsequent metastases. Likewise, thyroid transcription factor-1 was initially negative in the tumor but expression was present in metastatic lesions.
Subject(s)
Biomarkers, Tumor/analysis , Brain Neoplasms/chemistry , Brain Neoplasms/secondary , Carcinoma, Merkel Cell/chemistry , Carcinoma, Merkel Cell/secondary , Nuclear Proteins/analysis , Skin Neoplasms/chemistry , Transcription Factors/analysis , Aged , Biopsy , Brain Neoplasms/therapy , Carcinoma, Merkel Cell/therapy , Disease Progression , Humans , Immunohistochemistry , Keratin-20/analysis , Male , Predictive Value of Tests , Skin Neoplasms/pathology , Skin Neoplasms/therapy , Thyroid Nuclear Factor 1ABSTRACT
OBJECTIVE: To investigate the immunohistochemical expressions of p53, ki67, CK20 in superficial papillary urothelial neoplasms of the bladder and correlate them with histological grade, tumor progression and recurrence. METHODS: We selected samples of 43 patients with superficial transitional cell carcinoma of the bladder. They were divided into two groups, one called Recurrent (R), with 18 individuals, and other Non-Recurrent (NR), with 25. Multi-sampling blocks were prepared. The immunohistochemical technique employed was immunoperoxidase, and the antibodies were: p53: Novocastra (clone DO7) at a dilution of 1/100; Ki67: Spring (clone SP6) at a dilution of 1/100; and CK20: Dako (clone K20 .8) at a dilution of 1/50. RESULTS: The expression of p53 was observed in 11 cases, six in the Recurrent group and five in the Non-Recurrent, all high-grade tumors (p = 0.0001). The histological progression occurred in six patients (p = 0.0076). Of the 18 Recurrent cases, six showed immunoreactivity for p53 and 12 were negative for this antibody (p = 0.1715). Ki67 was positive in 17 of the 18 cases from the Recurrent group (p = 0.0001) and, from 20 high-grade tumors, 18 showed reaction to this antibody (p = 0.0001). Of the 18 individuals who had recurrence, 13 showed anomalous expression for CK20 (p = 0.0166). In high-grade carcinomas, of the 20 cases, 16 showed anomalous expression for this antibody, while 18 of the 23 patients with low-grade tumors showed normal expression for CK20 (p = 0.0002). CONCLUSION: The p53 showed good correlation with histological progression and histologic grade. Ki67 was strongly associated with recurrence and histological grade, and CK20 was also associated with these variables.
Subject(s)
Carcinoma, Transitional Cell/metabolism , Keratin-20/biosynthesis , Ki-67 Antigen/biosynthesis , Tumor Suppressor Protein p53/biosynthesis , Urinary Bladder Neoplasms/metabolism , Adult , Aged , Aged, 80 and over , Carcinoma, Transitional Cell/pathology , Carcinoma, Transitional Cell/surgery , Disease Progression , Female , Humans , Male , Middle Aged , Neoplasm Grading , Neoplasm Recurrence, Local/epidemiology , Prognosis , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/surgeryABSTRACT
An 80-year-old Caucasian male patient was referred for evaluation of a rapidly growing, asymptomatic, erythematous nodule measuring 2 cm in diameter on his left cheek. The lesion had been present for four months. Dermoscopy revealed a homogeneous pink background with polymorphous telangiectatic vessels. Histopathology showed tumors in the deep dermis and subcutis composed of round cells with scant cytoplasm. Immunohistochemical staining was positive for CK20 confirming the diagnosis of Merkel cell carcinoma.
Subject(s)
Carcinoma, Merkel Cell/pathology , Facial Neoplasms/pathology , Skin Neoplasms/pathology , Aged, 80 and over , Biomarkers, Tumor/analysis , Cheek , Humans , Keratin-20/analysis , MaleABSTRACT
Trichoepithelioma is a benign neoplasm that shares both clinical and histological features with basal cell carcinoma. It is important to distinguish these neoplasms because they require different clinical behavior and therapeutic planning. Many studies have addressed the use of immunohistochemistry to improve the differential diagnosis of these tumors. These studies present conflicting results when addressing the same markers, probably owing to the small number of basaloid tumors that comprised their studies, which generally did not exceed 50 cases. We built a tissue microarray with 162 trichoepithelioma and 328 basal cell carcinoma biopsies and tested a panel of immune markers composed of CD34, CD10, epithelial membrane antigen, Bcl-2, cytokeratins 15 and 20 and D2-40. The results were analyzed using multiple linear and logistic regression models. This analysis revealed a model that could differentiate trichoepithelioma from basal cell carcinoma in 36% of the cases. The panel of immunohistochemical markers required to differentiate between these tumors was composed of CD10, cytokeratin 15, cytokeratin 20 and D2-40. The results obtained in this work were generated from a large number of biopsies and resulted in the confirmation of overlapping epithelial and stromal immunohistochemical profiles from these basaloid tumors. The results also corroborate the point of view that trichoepithelioma and basal cell carcinoma tumors represent two different points in the differentiation of a single cell type. Despite the use of panels of immune markers, histopathological criteria associated with clinical data certainly remain the best guideline for the differential diagnosis of trichoepithelioma and basal cell carcinoma.
Subject(s)
Carcinoma, Basal Cell/diagnosis , Hair Diseases/diagnosis , Hair Follicle/pathology , Immunohistochemistry/methods , Skin Neoplasms/diagnosis , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Murine-Derived/metabolism , Biomarkers, Tumor/metabolism , Biopsy , Carcinoma, Basal Cell/metabolism , Child , Diagnosis, Differential , Female , Hair Diseases/metabolism , Hair Follicle/metabolism , Humans , Keratin-15/metabolism , Keratin-20/metabolism , Male , Middle Aged , Neprilysin/metabolism , Skin Neoplasms/metabolism , Stromal Cells/metabolism , Stromal Cells/pathology , Tissue Array Analysis , Young AdultABSTRACT
Gastrointestinal stromal tumor is the most common clinically significant mesenchymal neoplasm of the gastrointestinal tract. The expression of the intermediate filament cytokeratin in gastrointestinal stromal tumor is not frequently reported in the literature. The aim of this study was to investigate the immunohistochemical expression of several types of cytokeratin in a large number of cases (n=687), including a pan-cytokeratin marker (AE1/AE3 cocktail antibodies), high-molecular weight cytokeratins (34ßE12 antibody), and individual cytokeratins 8 (35ßH11 and CAM5.2 antibodies), 7, 14, and 20. Ki-67 antigen was used for the determination of cell proliferation index, and the correlation between Ki-67 and cytokeratin expression was evaluated. Cytokeratin expression was also correlated with several clinicopathologic parameters. The expression of pan-cytokeratin was observed in 24 (3.5%) cases, with variable intensity. Only 1 of 687 (0.1%) cases showed cytokeratin 14 expression. All 687 cases revealed no expression of high-molecular weight cytokeratins, cytokeratins 7, 8, and 20. No significant statistical association was found between AE1/AE3 immunoreactivity and several clinicopathologic parameters, including sex, tumor location and size, cell morphology, mitotic count, risk of aggressive behavior, and Ki-67 antigen cell proliferation index. However, statistical correlation between AE1/AE3 immunoreactivity and a higher age at diagnosis was detected. These results show that cytokeratin expression is not frequent in gastrointestinal stromal tumor, but caution is necessary to avoid erroneous diagnoses.
Subject(s)
Biomarkers, Tumor/biosynthesis , Gastrointestinal Neoplasms , Gene Expression Regulation, Neoplastic , Keratin-14/biosynthesis , Keratin-20/biosynthesis , Keratin-7/biosynthesis , Adult , Aged , Aged, 80 and over , Antibodies, Neoplasm/chemistry , Cell Proliferation , Female , Gastrointestinal Neoplasms/metabolism , Gastrointestinal Neoplasms/pathology , Humans , Immunohistochemistry/methods , Immunohistochemistry/standards , Ki-67 Antigen/biosynthesis , Male , Middle Aged , Retrospective StudiesABSTRACT
A case of gingival metastasis of adenocarcinoma of the colon is reported, the lesion being an early clinical indication of a primary malignant tumor. The diagnosis of metastatic lesion in the oral region is always challenging, both to clinician and to the pathologist, due to its rarity and complexity. In the present case, the clinical hypothesis was peripheral ossifying fibroma or pyogenic granuloma. Histologically, the biopsy tissue revealed a malignant neoplasm not connected to the mucosal surface. Immunohistochemically, the lesion was positive for 35ßH11 and cytokeratin 20 and focally positive for cytokeratin 7. Treatment involved excision of primary tumor and follow-up chemotherapy. The clinical, histological and immunohistochemical characteristics are discussed.
Subject(s)
Adenocarcinoma/secondary , Colonic Neoplasms/pathology , Gingival Neoplasms/secondary , Adenocarcinoma/metabolism , Adenocarcinoma/therapy , Adult , Biomarkers, Tumor/metabolism , Colonic Neoplasms/metabolism , Colonic Neoplasms/therapy , Combined Modality Therapy , Gingival Neoplasms/metabolism , Gingival Neoplasms/therapy , Humans , Keratin-20/metabolism , Keratin-7/metabolism , MaleABSTRACT
CONTEXT: Barrett's esophagus is characterized by the presence of goblet cells. However, when alcian-blue is utilized, another type of cells, called columnar blue cells, is frequently present in the distal esophagus of patients with endoscopic evidence of Barrett's esophagus. Cytokeratin 7 and 20 immunoreactivity has been previously studied in areas of intestinal metaplasia at the esophagogastric junction. However, the expression of these cytokeratins in columnar blue cells has not been characterized. OBJECTIVE: To compare the expression of cytokeratin 7 and 20 in goblet cells and columnar blue cells in patients with endoscopic evidence of Barrett's esophagus. METHODS: Biopsies from 86 patients with endoscopic evidence of Barrett's esophagus were evaluated. The biopsies were stained for cytokeratin 7 and 20. RESULTS: Goblet cells were present in 75 cases and columnar blue cells in 50 cases. Overall, cytokeratin 7 expression was similar in goblet cells and columnar blue cells (P = 0.25), while cytokeratin 20 was more common in goblet cells (P <0.001). In individuals with both cell types, however, cytokeratin 7 staining was the same in goblet and columnar blue cells in 95% of the cases, and cytokeratin 20 staining was the same in 77%. CONCLUSION: Goblet cells and columnar blue cells have similar immunohistochemical staining patterns for cytokeratins 7 and 20 in patients with endoscopic evidence of Barrett's esophagus.
Subject(s)
Barrett Esophagus/pathology , Goblet Cells/pathology , Keratin-20/metabolism , Keratin-7/metabolism , Alcian Blue , Barrett Esophagus/metabolism , Coloring Agents , Goblet Cells/metabolism , Humans , ImmunohistochemistryABSTRACT
We described 7 examples of Merkel cell carcinoma of the skin with eccrine and squamous differentiation. Five patients were men, and 2 were women; and their ages ranged from 63 to 81 years (mean age, 73 years). Six tumors arose in the head and neck; and one, on the sole of the right foot. Three tumors recurred locally, and 2 metastasized to the regional lymph nodes. No patient developed distant metastasis. Two patients died of unrelated causes. Five Merkel cell carcinomas showed classic cytology, and 2 were similar to small cell carcinomas of the lung. All 7 tumors showed small eccrine ducts, and 2 exhibited foci of squamous differentiation. The eccrine ducts label with cytokeratin 7 and carcinoembryonic antigen, whereas the predominant endocrine component displayed the characteristic paranuclear dot-like reactivity with cytokeratin 20 and was synaptophysin and chromogranin positive. The lymph node metastasis contained both eccrine ducts and squamous elements, suggesting that they are an integral component of the tumors. Eccrine differentiation in Merkel cell carcinomas similar to small cell carcinomas of the lung and extrapulmonary sites is an important feature in the differential diagnosis because eccrine differentiation has not been described in primary or metastatic small cell carcinomas. The prognosis of these Merkel cell carcinomas with divergent differentiation appears to be less aggressive than that of pure Merkel cell carcinomas. However, larger series of patients with longer follow-ups are needed to confirm this observation.
Subject(s)
Carcinoma, Merkel Cell/pathology , Cell Differentiation , Eccrine Glands/pathology , Skin Neoplasms/pathology , Aged , Aged, 80 and over , Carcinoma, Merkel Cell/diagnosis , Carcinoma, Merkel Cell/metabolism , Chromogranins/metabolism , Female , Humans , Keratin-20/metabolism , Male , Middle Aged , Prognosis , Skin Neoplasms/diagnosis , Skin Neoplasms/metabolism , Synaptophysin/metabolismABSTRACT
BACKGROUND: Colorectal cancer relapses or metastasizes in 30% of cases. Cytokeratin 20 is present in 95% of colorectal tumors and their metastases and could be used as a marker to detect tumor cells. AIM: To assess the usefulness and prognostic value of peripheral blood and bone marrow cytokeratin 20 determinations in patients with colorectal cancer. MATERIAL AND METHODS: Blood and bone marrow samples were obtained from 56 patients with colorectal cancer aged 26 to 77 years (31 females) before surgical procedure. They were followed for a mean of 22 months (range 2.9 to 72 months) after surgery. Blood and bone marrow from 45 patients without cancer and 35 healthy subjects were used as negative controls. Messenger RNA expression of cytokeratin 20 was studied by real time and nested polymerase chain reaction. RESULTS: Cytokeratin 20 was detected in 6% of controls and 41% of patients. There was no relation between cytokeratin 20 expression and age, gender, overall survival, tumor relapse, progression, localization or stage. CONCLUSIONS: Cytokeratin 20 determination is not useful as a marker of tumor progression or dissemination in patients with colorectal cancer.
Subject(s)
Biomarkers, Tumor/blood , Colorectal Neoplasms , Keratin-20/blood , Neoplasm Recurrence, Local/blood , Adult , Aged , Bone Marrow/chemistry , Bone Marrow/pathology , Case-Control Studies , Colorectal Neoplasms/blood , Colorectal Neoplasms/pathology , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Staging , Neoplastic Cells, Circulating , Prognosis , Reverse Transcriptase Polymerase Chain Reaction , Sensitivity and Specificity , Time FactorsABSTRACT
Pseudomyxoma peritonei (PMP) is a clinical condition initially thought to be related to ovarian mucinous tumors; however, immunohistochemistry and molecular biology techniques have convincingly made the link to appendiceal mucinous neoplasms, resulting in changes in histologic and clinical approaches. The objective of this study was to compare the immunohistochemical profile of ovarian tumors associated with PMP and intestinal mucinous ovarian neoplasms without PMP. The study was retrospective and included 28 intestinal ovarian mucinous tumors selected from the files of the Division of Surgical Pathology of the University of Sao Paulo Medical School, from 1996 to 2005. Seven cases were associated with PMP of disseminated peritoneal adenomucinosis-type and all presented borderline histology. Immunohistochemical staining for mucin genes products (MUC1, MUC2, MUC5AC, and MUC6), CK7, CK20, CA19.9, and CA125 were performed in tissue microarrays. Of note, we detected differences in the expression of MUC2 and CK20 between cases with and without PMP. Comparisons of borderline histology with that of benign/malignant tumors also revealed differences in MUC2 and CK20. Our results confirm that there is a distinct profile of intestinal ovarian tumors associated with pseudomyxoma, particularly with respect to the expression of the gel-forming mucin MUC2. The profile of borderline tumors, even in cases without PMP, was distinct from that of other primary mucinous tumors of the intestinal type, suggesting that borderline histology may represent a secondary tumor or a less aggressive variant of PMP. An appendiceal origin seems the most probable for this group of neoplasias.