Pro-COL11A1: A biomarker to predict malignant relapse of breast intraductal papillomas.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 540-540
Author(s):  
Javier Freire ◽  
Lucia Garcia-Berbel ◽  
Saioa Dominguez-Hormaetxe ◽  
Saray Pereda ◽  
Ana De Juan ◽  
...  
Keyword(s):  
Benign Lesion ◽  
Intraductal Papilloma ◽  
High Rate ◽  
Positive Staining ◽  
Complete Excision ◽  
Formalin Fixed Paraffin ◽  
Highly Sensitive ◽  
Formalin Fixed Paraffin Embedded ◽  
Formalin Fixed

540 Background: Breast cancer is currently the most frequent tumor among women. Despite the huge progress achieved in its early diagnosis, there are still many unsolved clinical issues, being the diagnosis, prognosis and treatment of papillary diseases (and specifically intraductal papilloma), one of the highest challenges. Because of its unpredictable clinical behavior, treatment of intraductal papilloma has generated a great controversy. Even though considered as a benign lesion, it presents high rate of malignant recurrence. This is the reason why there are clinicians supporting a complete excision of the papillary lesion, while others support an only expectant follow up. Previous results of our group have suggested that pro-Collagen 11 alpha 1 (pro-COL11A1) expression in cancer associated fibroblasts (CAFs) correlates with an infiltrating phenotype in breast lesions. We have analyzed the correlation between the differential expression of pro-COL11A1 in intraductal papilloma and their risk of malignant recurrence. Methods: Immunohistochemistry of pro-COL11A1 (clone 1E8.33, ONCOMATRIX, Bilbao, SPAIN) was performed in formalin fixed, paraffin embedded Core Needle Biopsy samples of 51 patients with intraductal papilloma. All patients had a minimum follow-up of 5 years. Results: Twenty-three out of 51 cases showed positive staining for COL11A1. Nine patients out of the positive cases relapsed as infiltrating carcinoma, two as intraductal papilloma and the rest had not recurred after five years of follow up. Only one case out of the 28 negative cases relapsed as invasive carcinoma. There were significant differences (p=0.0013) when comparing staining of individuals with malignant recurrence versus non recurrence and benign relapse patients, with a sensitivity of 90% and specificity of 66%. Conclusions: These data suggest that COL11A1 expression in CAFs is a highly sensitive biomarker to predict malignant relapse of intraductal papilloma. The low specificity might be biased by the complete excision of this lesion as the routine treatment or by a short follow-up of the patients.

scholarly journals Collagen Type XI Alpha 1 Expression in Intraductal Papillomas Predicts Malignant Recurrence

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Javier Freire ◽  
Lucia García-Berbel ◽  
Pilar García-Berbel ◽  
Saray Pereda ◽  
Ainara Azueta ◽  
...  
Keyword(s):  
Collagen Type ◽  
Benign Lesion ◽  
Intraductal Papilloma ◽  
High Rate ◽  
Positive Staining ◽  
Breast Lesions ◽  
Complete Excision ◽  
Clinical Behavior ◽  
Highly Sensitive

Despite the progress achieved in the treatment of breast cancer, there are still many unsolved clinical issues, being the diagnosis, prognosis, and treatment of papillary diseases, one of the highest challenges. Because of its unpredictable clinical behavior, treatment of intraductal papilloma has generated a great controversy. Even though considered as a benign lesion, it presents high rate of malignant recurrence. This is the reason why there are clinicians supporting a complete excision of the lesion, while others support an only expectant follow-up. Previous results of our group suggested that procollagen 11 alpha 1 (pro-COL11A1) expression correlates with infiltrating phenotype in breast lesions. We analyzed the correlation between expression of pro-COL11A1 in intraductal papilloma and their risk of malignant recurrence. Immunohistochemistry of pro-COL11A1 was performed in 62 samples of intraductal papilloma. Ten out 11 cases relapsed as carcinoma presents positive staining for COL11A1, while just 17 out of 51 cases with benign behaviour present immunostaining. There were significant differences (P<0.0001) when comparing patients with malignant recurrence versus nonmalignant relapse patients. These data suggest that pro-COL11A1 expression is a highly sensitive biomarker to predict malignant relapse of intraductal papilloma and it can be used as indicative factor for prevention programs.

Microsatellite instability evaluation: which test to use for endometrial cancer?

2021 ◽  
pp. jclinpath-2021-207723
Author(s):  
Paola Rafaniello-Raviele ◽  
Ilaria Betella ◽  
Alessandra Rappa ◽  
Davide Vacirca ◽  
Gianluca Tolva ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Microsatellite Instability ◽  
Automated System ◽  
Tissue Samples ◽  
Valuable Alternative ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Formalin Fixed ◽  
Mmr Proteins

AimsAnalysis of microsatellite instability (MSI) is strongly recommended in endometrial cancer (EC) and colorectal cancer to screen for Lynch syndrome, to predict prognosis and to determine optimal treatment and follow-up. In a large monoinstitutional series of ECs, we evaluated the reliability and accuracy of Idylla assay, a rapid, fully automated system to detect MSI, and we compared its performance with two routine reference methods.MethodsWe evaluated MSI status in 174 formalin-fixed, paraffin-embedded EC tissue samples using immunohistochemistry (IHC) for mismatch repair (MMR) proteins and Idylla assay. Samples with discordant or equivocal results were analysed with a third technique, the Promega MSI kit.ResultsIdylla MSI assay and IHC were highly concordant (overall agreement: 154/170=90.59%, 95% CI 85.26% to 94.12%). However, in four samples, MMR-IHC staining was equivocal; moreover, 16 cases showed discordant results, that is, MMR deficient using IHC and microsatellite stable using Idylla. These 20 samples were reanalysed using the MSI-Promega kit, which showed the same results of Idylla assay in 18/20 cases (overall agreement: 90%, 95% CI 69.90% to 97.21%).ConclusionsOur results suggest that IHC is an efficient method to determine MMR status in ECs. However, the Idylla MSI assay is a rapid and reliable tool to define MSI status, and it could represent a valuable alternative to conventional MSI-PCR methods.

PDL-1 and immunohistochemistry markers in esophageal adenocarcinoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15567-e15567
Author(s):  
Dawn E. Jaroszewski ◽  
Joanne Xiu ◽  
Zoran Gatalica ◽  
Staci Beamer ◽  
Melissa Stanton ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Esophageal Adenocarcinoma ◽  
Neoadjuvant Treatment ◽  
Formalin Fixed Paraffin ◽  
Ffpe Tumor ◽  
Ffpe Samples ◽  
Formalin Fixed Paraffin Embedded ◽  
Formalin Fixed

e15567 Background: Esophageal adenocarcinoma (EAC) prognosis is poor and there is a need to identify patients that benefit most from neoadjuvant therapy. To examine the association of various biomarkers with clinical outcomes in neoadjuvant treatment of EAC, we retrospectively evaluated the biomarker expression (TS, ERCC1, TOPO1, PD-L1, PD-1) in patient matched formalin-fixed paraffin-embedded (FFPE) tumor samples. Methods: Immunohistochemistry of TS (TS106/4H4B1) , ERCC1 (Ab. 8F1), TOPO1 (1D6), PD-L1 (both 22c3 and SP142), PD-1 (NAT105), and chromogenic in-situ hybridization (CISH) of Her2 were performed on FFPE samples from 35 patients across 2 institutions at time of EAC diagnosis and after treatment when available. Retrospective clinical data and survival (5/2006-1/2016) was analyzed with a mean follow up of 110 months (range 22-306). Results: Overexpression (pre/post-treatment) of TS (60%/54%), ERCC1 (69%/16%), TOPO1 (74%/50%), PD-1 (54%/63%), PD-L1 (SP142) (2.9%/4%), PD-L1 (22c3) (0%/4%) and amplification of Her2 (18%/23%) were observed. Pretreatment observed PD-L1 levels were lower in our study (3%) when compared to other studies in EAC specimens (35%). Immunohistochemistry and changes observed after chemoradiation are reviewed in Table. No markers had significant correlation with prognosis however TS negative expression showed a non-significant (p=0.15) trend towards improved survival. Conclusions: Analyzing biomarkers in our neoadjuvant EAC cohort demonstrated a lower than expected PD-L1 positivity. In the largest cohort, to our knowledge, of patient matched FFPE tumor samples, we did not observe a statistically significant association between TS, ERCC1, TOPO1, PD-L1, or PD-1 with improved clinical outcomes. [Table: see text]

Immunohistochemical Demonstration of Desmin in Canine Smooth Muscle Tumors

1987 ◽  
Vol 24 (3) ◽  
pp. 211-215 ◽  
Author(s):  
C. B. Andreasen ◽  
E. A. Mahaffey
Keyword(s):  
Smooth Muscle ◽  
Positive Staining ◽  
Negative Results ◽  
Formalin Fixed Paraffin ◽  
Smooth Muscle Tumors ◽  
Formalin Fixed Paraffin Embedded ◽  
Immunohistochemical Methods ◽  
Formalin Fixed ◽  
Immunohistochemical Identification ◽  
Avidin Biotin Complex

Sections of formalin-fixed, paraffin-embedded canine leiomyomas, leiomyosarcomas, or fibrosarcomas were examined by immunohistochemical methods for the presence of desmin. Twenty-two leiomyomas and leiomyosarcomas were stained using the avidin-biotin complex technique, and 14 samples demonstrated positive staining for desmin. The eight negative results obtained may reflect differences in fixation or the affinity of the primary antibody for the tissues examined. Desmin was specific for myogenic tissues. Five canine fibrosarcomas examined immunohistochemically were all negative for desmin staining. The results indicate that desmin is a useful marker for immunohistochemical identification of canine leiomyomas and leiomyosarcomas.

scholarly journals Immunohistochemical Staining Patterns of Canine Meningiomas and Correlation with Published Immunophenotypes

2002 ◽  
Vol 39 (3) ◽  
pp. 311-321 ◽  
Author(s):  
K. F. Barnhart ◽  
J. Wojcieszyn ◽  
R. W. Storts
Keyword(s):  
Immunohistochemical Staining ◽  
Neuron Specific Enolase ◽  
Positive Staining ◽  
Neoplastic Cells ◽  
Vimentin Expression ◽  
Immunohistochemical Markers ◽  
Formalin Fixed Paraffin ◽  
Tumor Group ◽  
Formalin Fixed Paraffin Embedded ◽  
Formalin Fixed

This study examined immunohistochemical staining patterns for several meningioma variants involving either the brain or spinal cord of dogs. Formalin-fixed, paraffin-embedded tissue from 15 tumors was obtained. The selected tumor group included seven meningothelial, three transitional, two malignant (anaplastic), one myxoid, one papillary, and one osteomatous meningiomas. Tumors were evaluated for reactivity to the following six immunohistochemical markers: vimentin, pancytokeratin, glial fibrillary acidic protein (GFAP), S100, neuron-specific enolase (NSE), and synaptophysin. Vimentin expression was detected in all meningiomas, and 14 of 15 tumors demonstrated intense vimentin staining in more than 50% of the neoplastic cells. Pancytokeratin expression was present in 11 of 15 neoplasms; however, positive staining frequently was focal and often involved a small percentage of the neoplastic cells. GFAP expression was detected in a single, anaplastic meningioma. Although expression of NSE and S100 was detected in 12 of 25 meningiomas, the intensity of the staining and the percentage of positive neoplastic cells was highly variable. Synaptophysin was uniformly negative. These results will help to establish immunohistochemical profiles for meningiomas that will improve our ability to correctly differentiate these neoplasms of meningeal origin from central nervous system tumors originating from other sites.

A103 Immunostaining in the Diagnosis of Adrenal Cortical Tumors

2002 ◽  
Vol 126 (2) ◽  
pp. 170-172 ◽  
Author(s):  
Timothy S. Loy ◽  
Roy W. Phillips ◽  
Chadwick L. Linder
Keyword(s):  
Differential Diagnosis ◽  
Metastatic Carcinoma ◽  
Serous Carcinoma ◽  
Positive Staining ◽  
Adrenal Metastases ◽  
Cortical Cells ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Adrenal Cortical Cells ◽  
Formalin Fixed

Abstract Context.—The monoclonal antibody A103 recognizes an antigen on melanoma cells known as Melan-A or MART-1. Recent studies have shown that A103 also reacts with adrenal cortical cells and may be useful in the diagnosis of adrenal cortical tumors. However, only small numbers of some of the tumors in the differential diagnosis of adrenal cortical neoplasms have been studied. Objective.—To study the specificity of A103 immunohistochemistry in a large number of tumors in the differential diagnosis of adrenal cortical neoplasms. Design.—Formalin-fixed, paraffin-embedded tissue from 21 adrenal cortical tumors, 16 cases of metastatic carcinoma to the adrenal, 10 pheochromocytomas, and 269 extra-adrenal carcinomas was evaluated for A103 immunoreactivity using a commercially available antibody (Novocastra, Newcastle, UK). Results.—Positive staining was seen in all of the adrenal cortical tumors but in none of the adrenal metastases or pheochromocytomas. In the 269 extra-adrenal carcinomas, A103 immunoreactivity was limited to a single ovarian serous carcinoma. Conclusion.—A103 immunostaining is useful in distinguishing adrenal cortical neoplasms from other carcinomas and pheochromocytoma.

scholarly journals Role of Immunohistochemistry Markers (p53 and CEA), in Study of Colorectal Tumours

2021 ◽  
pp. 94-106
Author(s):  
Sapam Chingkhei Lakpa ◽  
R. Vinoth Kumar ◽  
Mary Lilly
Keyword(s):  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
High Rate ◽  
Common Cancer ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
P53 Tumour Suppressor Gene ◽  
Formalin Fixed ◽  
Colorectal Tumours

Colorectal cancer is the third most common cancer in men and the second in women globally. There is a marked variation in the incidence of colorectal carcinoma worldwide, where western countries having high rate compared to others. p53 tumour suppressor gene is one of the most intensively studied tumour markers in the colorectal tumours. Two markers were used, p53 (oncoprotein p53) and CEA (carcinoembryonic antigen) in the study. The 102 cases of paraffin-embedded samples were processed for the immunohistochemistry examination. After the analysis of the selected patients regarding the antibodies distribution, statistical analysis was performed. The current study showed that there was a statistically significant correlation existing between p53 and CEA in each tumour type irrespective of its histological grades. The immunohistochemistry (IHC) was performed on 4-µm thick sections from 10% formalin- fixed paraffin-embedded tissue blocks.

Comparative study of two PD-L1 expression assays in patients with non-small cell lung cancer (NSCLC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20581-e20581 ◽  
Author(s):  
Zheng Feng ◽  
Michael Schlichting ◽  
Christoph Helwig ◽  
Vikram K. Chand ◽  
Arnold Gelb ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Dynamic Range ◽  
Low Frequency ◽  
Formalin Fixed Paraffin ◽  
Broad Dynamic Range ◽  
Formalin Fixed Paraffin Embedded ◽  
Commercial Source ◽  
Formalin Fixed ◽  
Clinical Trial Information

e20581 Background: Response to anti–PD-L1/PD-1 therapy in patients with NSCLC has been associated with tumor PD-L1 expression. Avelumab is a fully human anti‒PD-L1 IgG1 antibody that has shown antitumor activity in advanced NSCLC, with a trend for greater efficacy in patients with PD-L1+ vs PD-L1– NSCLC tumors, as assessed using a proprietary PD-L1 assay in development (Dako, Carpinteria, CA; based on antibody clone 73-10, Merck KGaA, Darmstadt, Germany). This study compares the analytical performance of the 73-10 assay with the FDA-approved PD-L1 IHC 22C3 pharmDx diagnostic assay (Dako) in NSCLC tumors. Methods: Formalin-fixed paraffin-embedded NSCLC tumor samples were obtained from a commercial source and from a study of first-line (1L) avelumab in patients with advanced NSCLC (NCT01772004). Tumor membrane PD-L1 expression was assessed with the 73-10 and 22C3 assays by immunohistochemistry. Correlation between assays was determined at different PD-L1 cut-off levels. Results: In initial staining of commercial NSCLC samples, the 73-10 assay showed a broad dynamic range. Of 148 commercial samples, the 73-10 assay with ≥1%, ≥50% and ≥80% cut-offs classified 64.2%, 36.5% and 23.6% of samples as PD-L1+, respectively, whereas 20.3% were PD-L1+ with the 22C3 assay at a pre-specified ≥50% cut-off. The overall percentage agreement between assays was 83.8% using the ≥50% cut-off for both assays, and 93.9% using the ≥80% cut-off for 73-10 and ≥50% for 22C3. In follow-up studies, 83 study samples from the 1L NSCLC cohort were evaluable with both assays. With the 73-10 assay at ≥1%, ≥50%, and ≥80% cut-offs, 79.5%, 45.8%, and 31.3% of study tumors, respectively, were PD-L1+; with the 22C3 assay at ≥1% and ≥50% cut-offs, 59.0% and 21.7% were PD-L1+. Conclusions: Using a high tumor cell PD-L1 staining cut-off, the 73-10 and 22C3 assays showed highly concordant staining of NSCLC samples, with similar sensitivity observed with an ≥80% cut-off for 73-10 and ≥50% for 22C3. Using a low frequency of tumor PD-L1 expression, data suggested that the 73-10 assay had greater sensitivity than the 22C3 assay. These results provide a rationale for additional studies using the 73-10 assay at various cut-offs within the avelumab trial program. Clinical trial information: NCT01772004.

scholarly journals Evaluation of PCR in Detection of Mycobacterium tuberculosis from Formalin-Fixed, Paraffin-Embedded Tissues: Comparison of Four Amplification Assays

1998 ◽  
Vol 36 (6) ◽  
pp. 1512-1517 ◽  
Author(s):  
Giulia Marchetti ◽  
Andrea Gori ◽  
Lidia Catozzi ◽  
Luca Vago ◽  
Manuela Nebuloni ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
False Negative ◽  
Pcr Amplification ◽  
Positive Culture ◽  
Single Copy ◽  
High Rate ◽  
Antigen Gene ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Formalin Fixed

We compared the sensitivities and specificities of four nested PCR assays for the detection of Mycobacterium tuberculosis from formalin-fixed, paraffin-embedded tissues. Thirty-seven autopsy samples from human immunodeficiency virus-positive patients were analyzed: 15 were M. tuberculosis positive, 11 served as negative controls, and 11 were Ziehl-Neelsen positive without cultural confirmation of M. tuberculosis. Three genomic sequences (mtp40, 65-kDa antigen gene, and IS6110) with different molecular masses and numbers of repetitions within the M. tuberculosis genome were targeted. On the IS6110 sequence, two fragments of different sizes (106 and 123 bp, respectively) were amplified with two separate pairs of primers. The highest sensitivity rates were obtained by amplifying the highly repetitive IS6110 insertion sequence, and the different primers tested showed a sensitivity ranging from 80 to 87%. Amplification of the large 223-bp fragment of themtp40 sequence present in a single copy in the M. tuberculosis genome yielded a high rate of false-negative results, ranging from 66 to 80%. A poor sensitivity (from 47 to 60%) was also shown by PCR amplification of the 142-bp 65-kDa antigen gene. All the PCRs except that for the 65-kDa antigen gene showed a specificity of 100%. Moreover, different results were obtained with different dilutions of DNA, and DNA concentrations of 1 and 3 μg yielded the highest sensitivities depending upon which protocol was used. Application of the PCRs to the Ziehl-Neelsen-positive, culture-negative samples confirmed the sensitivities of the PCRs obtained with the control samples. In conclusion, PCR can successfully be used to detect M. tuberculosis from paraffin-embedded tissues and can be particularly useful in the validation of a diagnosis of tuberculosis in clinical settings in which the diagnosis is uncertain. However, the efficacy of PCR strictly depends on several amplification parameters such as DNA concentration, target DNA size, and the repetitiveness of the amplified sequence.

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