Evaluation of MCL-1 as a prognostic factor in canine mammary gland tumors.

Myeloid cell leukemia-1 (MCL-1), which belongs to the anti-apoptotic B cell lymphoma-2 family protein, is overexpressed in various cancers and is associated with cell immortality, malignant transformation, chemoresistance, and poor prognosis in humans. However, the significance of MCL-1 in canine mammary gland tumors (MGTs) remains unknown. This study aimed to examine MCL-1 expression in normal canine mammary glands and tumors and to assess its correlation with clinical and histologic variables. In total, 111 samples were examined, including 12 normal mammary gland tissues, 51 benign MGTs, and 48 malignant MGTs. Immunohistochemistry revealed that 53% of benign tumors and 75% of malignant tumors exhibited high MCL-1 expression, whereas only 8% of normal mammary glands exhibited high MCL-1 expression. High MCL-1 expression correlated with tumor malignancy (p < 0.001), large tumor size (> 3 cm) (p = 0.005), high Ki-67 expression (p = 0.046), and metastasis (p = 0.027). Survival curve analysis of dogs with malignant MGTs demonstrated a significant association between high MCL-1 expression and shorter median overall survival (p = 0.027) and progression-free survival (p = 0.014). Our study identified MCL-1 as a prognostic factor and potential therapeutic target in canine MGTs.

Immunohistochemistry staining of Eag1 and p16/Ki-67 can help improve the management of patients with cervical intraepithelial Neoplasia after cold knife conversion.

BACKGROUND: Immunohistochemistry (IHC) is widely used in the management of patients with cervical intraepithelial neoplasia (CIN) but still has many limitations in clinical practice. We analyzed the correlation of new biomarkers with the severity of CIN and follow-up outcomes in patients after conization to improve the management of patients with CIN. METHODS: IHC staining of Eag1 and p16/Ki-67 was performed on cervical tissue sections from 234 patients with suspected CIN2/3. After a series of follow-ups, including human papillomavirus (HPV) test and thinprep cytologic test (TCT) for 1-2 years, the outcomes were collected. IHC scores of biomarkers and follow-up results were used to analyze the correlation and assess the diagnostic efficiency of biomarkers. RESULTS: The IHC staining intensity of Eag1 and p16/Ki-67 was significantly different from that of the CIN1-3 groups (p < 0.05). Eag1 expression scores were significantly different in the distribution between the two follow-up groups (p < 0.001). ROC curves based on the correlations between the follow-up outcomes and the Eag1 scores and IS of p16/ki-67 showed that Eag1 had a greater AUC (0.767 vs. 0.666). Logistic regression analysis of the combination of biomarkers revealed a greater AUC value than any single biomarker. CONCLUSIONS: Eag1 expression was significantly correlated with CIN grade and follow-up outcomes after conization. IHC staining of combinations of biomarkers of Eag1, p16 and Ki-67 may help us to improve the ability to identify risk groups with abnormal follow-up outcomes after treatment for CIN.

Natural Killer Cell Presence in Antibody-Mediated Rejection.

Transcript analyses highlight an important contribution of natural killer (NK) cells to microvascular inflammation (MVI) in antibody-mediated rejection (ABMR), but only few immunohistologic studies have quantified their spatial distribution within graft tissue. This study included 86 kidney transplant recipients who underwent allograft biopsies for a positive donor-specific antibody (DSA) result. NK cells were visualized and quantified within glomeruli and peritubular capillaries (PTC), using immunohistochemistry for CD34 alongside CD16/T-bet double-staining. Staining results were analyzed in relation to histomorphology, microarray analysis utilizing the Molecular Microscope Diagnostic System, functional NK cell genetics, and clinical outcomes. The number of NK cells in glomeruli per mm2 glomerular area (NKglom) and PTC per mm2 cortical area (NKPTC) was substantially higher in biopsies with ABMR compared to those without rejection, and correlated with MVI scores (NKglom Spearman's correlation coefficient [SCC] = 0.55, p < 0.001, NKPTC 0.69, p < 0.001). In parallel, NK cell counts correlated with molecular classifiers reflecting ABMR activity (ABMRprob: NKglom 0.59, NKPTC 0.75) and showed a trend towards higher levels in association with high functional FCGR3A and KLRC2 gene variants. Only NKPTC showed a marginally significant association with allograft function and survival. Our immunohistochemical results support the abundance of NK cells in DSA-positive ABMR.

Correlation of PD-L1 expression with CD8+ T cells and oxidative stress-related molecules NRF2 and NQO1 in esophageal squamous cell carcinoma.

Oxidative stress and the immune microenvironment both contribute to the pathogenesis of esophageal squamous cell carcinoma (ESCC). However, their interrelationships remain poorly understood. We aimed to examine the status of key molecules involved in oxidative stress and the immune microenvironment, as well as their relationships with each other and with clinicopathological features and prognosis in ESCC. The expression of programmed death-ligand 1 (PD-L1), CD8, nuclear factor erythroid-2 related factor-2 (NRF2), and NAD(P)H quinone oxidoreductase 1 (NQO1) was detected using immunohistochemistry in tissue samples from 176 patients with ESCC. We employed both combined positive score (CPS) and tumor proportion score (TPS) to evaluate PD-L1 expression and found a positive correlation between CPS and TPS. Notably, PD-L1 expression, as assessed by either CPS or TPS, was positively correlated with both NRF2 nuclear score and NQO1 score in stage II-IV ESCC. We also observed a positive correlation between the density of CD8+ T cells and PD-L1 expression. Furthermore, high levels of PD-L1 CPS, but not TPS, were associated with advanced TNM stage and lymph node metastases. Moreover, both PD-L1 CPS and the nuclear expression of NRF2 were found to be predictive of shorter overall survival in stage II-IV ESCC. By using the Mandard-tumor regression grading (TRG) system to evaluate the pathological response of tumors to neoadjuvant chemotherapy (NACT), we found that the TRG-5 group had higher NRF2 nuclear score, PD-L1 CPS, and TPS in pre-NACT biopsy samples compared with the TRG-3 + 4 group. The NQO1 scores of post-NACT surgical specimens were significantly higher in the TRG-5 group than in the TRG 3 + 4 group. In conclusion, the expression of PD-L1 is associated with aberrant NRF2 signaling pathway, advanced TNM stage, lymph node metastases, and unfavorable prognosis. The dysregulation of PD-L1 and aberrant activation of the NRF2 signaling pathway are implicated in resistance to NACT. Our findings shed light on the complex interrelationships between oxidative stress and the immune microenvironment in ESCC, which may have implications for personalized therapies and improved patient outcomes.

Analysis of Expression of the ANG1, CaSR and FAK Proteins in Uterine Fibroids.

Understanding the molecular factors involved in the development of uterine myomas may result in the use of pharmacological drugs instead of aggressive surgical treatment. ANG1, CaSR, and FAK were examined in myoma and peripheral tissue samples taken from women after myoma surgery and in normal uterine muscle tissue samples taken from the control group. Tests were performed using tissue microarray immunohistochemistry. No statistically significant differences in ANG1 expression between the tissue of the myoma, the periphery, and the normal uterine muscle tissue of the control group were recorded. The CaSR value was reduced in the myoma and peripheral tissue and normal in the group of women without myomas. FAK expression was also lower in the myoma and periphery compared to the healthy uterine myometrium. Calcium supplementation could have an effect on stopping the growth of myomas.

First Immunohistochemical Demonstration of the Expression of a Type-2 Vomeronasal Receptor, V2R2, in Wild Canids.

The mammalian vomeronasal system enables the perception of chemical signals crucial for social communication via the receptor families V1R and V2R. These receptors are linked with the G-protein subunits, Gαi2 and Gαo, respectively. Exploring the evolutionary pathways of V1Rs and V2Rs across mammalian species remains a significant challenge, particularly when comparing genomic data with emerging immunohistochemical evidence. Recent studies have revealed the expression of Gαo in the vomeronasal neuroepithelium of wild canids, including wolves and foxes, contradicting predictions based on current genomic annotations. Our study provides detailed immunohistochemical evidence, mapping the expression of V2R receptors in the vomeronasal sensory epithelium, focusing particularly on wild canids, specifically wolves and foxes. An additional objective involves contrasting these findings with those from domestic species like dogs to highlight the evolutionary impacts of domestication on sensory systems. The employment of a specific antibody raised against the mouse V2R2, a member of the C-family of vomeronasal receptors, V2Rs, has confirmed the presence of V2R2-immunoreactivity (V2R2-ir) in the fox and wolf, but it has revealed the lack of expression in the dog. This may reflect the impact of domestication on the regression of the VNS in this species, in contrast to their wild counterparts, and it underscores the effects of artificial selection on sensory functions. Thus, these findings suggest a more refined chemical detection capability in wild species.

The Role of SCARA5 as a Potential Biomarker in Squamous Cell Carcinoma of the Lung.

Lung cancer is the leading cause of cancer-related deaths in the western world. Squamous cell carcinoma is one of the most common histological subtypes of this malignancy. For squamous cell carcinoma of the lung (LSCC), prognostic and predictive markers still are largely missing. In a previous study, we were able to show that the expression of THSD7A shows an association with unfavorable prognostic parameters in prostate cancer. There is also a link to a high expression of FAK. There is incidence that SCARA5 might be the downstream gene of THSD7A. Furthermore, there is evidence that SCARA5 interacts with FAK. We were interested in the role of SCARA5 as a potential biomarker in LSCC. Furthermore, we wanted to know whether SCARA5 expression is linked to THSD7A positivity and to the expression level of FAK. For this reason, we analyzed 101 LSCC tumors by immunohistochemistry. Tissue microarrays were utilized. No significant association was found between SCARA5 expression and overall survival or clinicopathological parameters. There was also no significant association between THSD7A positivity and SCARA5 expression level. Moreover, no significant association was found between FAK expression level and SCARA5 expression level. SCARA5 seems not to play a major role as a biomarker in squamous cell carcinoma of the lung.

Analytical Post-Embedding Immunogold-Electron Microscopy with Direct Gold-Labelled Monoclonal Primary Antibodies against RIBEYE A- and B-Domain Suggests a Refined Model of Synaptic Ribbon Assembly.

Synaptic ribbons are the eponymous specializations of continuously active ribbon synapses. They are primarily composed of the RIBEYE protein that consists of a unique amino-terminal A-domain and carboxy-terminal B-domain that is largely identical to the ubiquitously expressed transcriptional regulator protein CtBP2. Both RIBEYE A-domain and RIBEYE B-domain are essential for the assembly of the synaptic ribbon, as shown by previous analyses of RIBEYE knockout and knockin mice and related investigations. How exactly the synaptic ribbon is assembled from RIBEYE subunits is not yet clear. To achieve further insights into the architecture of the synaptic ribbon, we performed analytical post-embedding immunogold-electron microscopy with direct gold-labelled primary antibodies against RIBEYE A-domain and RIBEYE B-domain for improved ultrastructural resolution. With direct gold-labelled monoclonal antibodies against RIBEYE A-domain and RIBEYE B-domain, we found that both domains show a very similar localization within the synaptic ribbon of mouse photoreceptor synapses, with no obvious differential gradient between the centre and surface of the synaptic ribbon. These data favour a model of the architecture of the synaptic ribbon in which the RIBEYE A-domain and RIBEYE B-domain are located similar distances from the midline of the synaptic ribbon.

Stanniocalcin-2 expression in glioblastoma - A novel prognostic biomarker: An observational study.

The objective of this study was to assess the prognostic relevance of Stanniocalcin-2 (STC2) expression, as determined via immunohistochemistry in tumor tissue, in a cohort of 83 patients diagnosed with glioblastoma who underwent maximal safe surgical resection followed by radiotherapy concurrent with adjuvant temozolomide. STC2 expression levels were categorized using a 3-tiered semiquantitative system: negative expression (level 0-), low expression (level 1+), and high expression (levels 2 + and 3+). Patients were categorized into 2 distinct groups according to their STC2 expression levels: negative STC2 (-/+) and positive STC2 (++/+++). The primary outcome measure was the relationship between STC2 expression and progression-free survival (PFS), with overall survival (OS) serving as the secondary endpoint. Kaplan-Meier survival analysis confirmed that patients exhibiting high STC2 expression had significantly shorter OS (8 vs 20 months, P < .001) and PFS (6 vs 18 months, P < .001) than those with low or negative STC2 expression. Multivariate analysis revealed that STC2 expression was an independent prognostic factor for both OS (hazard ratio: 0.4; 95% confidence interval: 0.2-0.8; P < .05) and PFS (hazard ratio: 0.3; 95% confidence interval: 0.2-0.4; P < .05) in patients with glioblastoma. Furthermore, elevated STC2 expression in GBM was correlated with several established aggressive clinicopathological characteristics, including advanced age (≥65 years), low ECOG PS (≥2), and isocitrate dehydrogenase mutation negativity. These findings underscore that heightened STC2 expression within the tumor tissue of GBM patients functions as an adverse prognostic marker, correlating with an elevated risk of progression and reduced OS. Therapeutic interventions targeting the AKT-mTOR, ERK1-2, and mitogen-activated protein kinase pathways as well as immune checkpoint inhibitors and vascular endothelial growth factor blockade, as well as potential forthcoming antibody-drug conjugates targeting the STC2 molecule, have the potential to broaden the scope of combined treatment strategies.

An elderly case of paraneoplastic anti-NMDA receptor encephalitis associated with large cell neuroendocrine carcinoma of the lung.

BACKGROUND: Recent studies have suggested that N-methyl-D-aspartate (NMDA) receptors are involved in the cell proliferation in several tumors. However, there have been no reports demonstrating the expression of NR1 subunit of the NMDA receptor in large cell neuroendocrine carcinoma (LCNEC). CASE PRESENTATION: Here, we report the first elderly case of paraneoplastic anti-NMDA receptor encephalitis associated with LCNEC of the lung with NR1 expression. Of note, NR1 subunit expression in the tumor cells of the present case was confirmed by immunohistochemistry (IHC). Radiation therapy and immunotherapies, such as corticosteroids and intravenous immunoglobulin (IVIG), shrank the tumors and improved neurological symptoms in the present case. Additionally, we also confirmed the expression of NR1 in the tumor cells obtained from three other cases with LCNEC of the lung at our hospital by IHC. CONCLUSION: Our IHC results indicate that LCNEC generally expresses NR1 subunit and NMDA receptor may be involved in the tumor development and growth.

Expression of Intracellular Galectin-8 and -9 in Endometrial Cancer.

Endometrial cancer (EC) is a common gynecological cancer worldwide. Treatment has been improved in recent years; however, in advanced stages, therapeutic options are still limited. The expression of galectins is increased in several tumor types and that they are involved in important cell processes. Large studies on endometrial cancer are still pending; Specimens of 225 patients with EC were immunohistochemically stained with antibodies for Gal-8 and Gal-9. Expression was correlated with histopathological variables. The cytosolic expression of both galectins is associated with grading and survival. Cytosolic Galectin-8 expression is a positive prognostic factor for overall survival (OS) and progression-free survival (PFS), while nuclear Gal-8 expression correlates only to OS. The cytosolic presence of Galectin-9 is correlated with a better prognosis regarding OS. Our results suggest that expression of both galectins is associated with OS and PFS in EC. Further studies are needed to understand the underlying molecular mechanisms.

Study on the Relationship Between MRI Functional Imaging and Multiple Immunohistochemical Features of Glioma: A Noninvasive and More Precise Glioma Management.

Objective: To investigate the performance of diffusion-tensor imaging (DTI) and hydrogen proton magnetic resonance spectroscopy (1H-MRS) parameters in predicting the immunohistochemistry (IHC) biomarkers of glioma. Methods: Patients with glioma confirmed by pathology from March 2015 to September 2019 were analyzed, the preoperative DTI and 1H-MRS images were collected, apparent diffusion coefficient (ADC) and fractional anisotropy (FA), in the lesion area were measured, the relative values relative ADC (rADC) and relative FA (rFA) were obtained by the ratio of them in the lesion area to the contralateral normal area. The peak of each metabolite in the lesion area of 1H-MRS image: N-acetylaspartate (NAA), choline (Cho), and creatine (Cr), and metabolite ratio: NAA/Cho, NAA/(Cho + Cr) were selected and calculated. The preoperative IHC data were collected including CD34, Ki-67, p53, S-100, syn, vimentin, NeuN, Nestin, and glial fibrillary acidic protein. Results: One predicting parameter of DTI was screened, the rADC of the Ki-67 positive group was lower than that of the negative group. Two parameters of 1H-MRS were found to have significant reference values for glioma grades, the NAA and Cr decreased as the grade of glioma increased, moreover, Ki-67 Li was negatively correlated with NAA and Cr. Conclusion: NAA and Cr have potential application value in predicting glioma grades and tumor proliferation activity. Only rADC has predictive value for Ki-67 expression among DTI parameters.

PD-L2 Expression in Breast Cancer Promotes Tumor Development and Progression.

Background: This work focused on investigating the role of programmed death ligand 2 (PD-L2) in the progression of breast cancer by utilizing breast cancer specimens and cells. Materials and Methods: The serum levels of soluble PD-L2 (sPD-L2) in breast cancer patients and healthy individuals were analyzed by means of the enzyme-linked immunosorbent assay, and the PD-L2 levels within 416 resected breast cancer specimens were assessed through immunohistochemistry. Concurrently, in vitro cell experiments and in vivo animal experiments were carried out to analyze the relationship between PD-L2 and the invasion and migration of breast cancer. Results: The concentration of sPD-L2 in breast cancer patients significantly increased compared to that in the control groups. Additionally, breast cancer patients with high concentrations of sPD-L2 had higher Ki67 values (≥30%) and tumor grades. PD-L2 was expressed in 79.09% of the cancer samples, which exhibited a positive correlation with the progesterone receptor (PR) and the human epidermal growth factor receptor 2 (HER2). Furthermore, we discovered that knockdown of PD-L2 inhibited the migratory and invasive abilities of both MCF-7 and MDA-MB231 cells. Conclusion: Our findings demonstrated that knockdown of PD-L2 suppressed tumor growth, providing novel insights into important biological functions.

Endometrial serous carcinoma with a corded and hyalinized pattern: a clinicopathological and molecular analysis.

A corded and hyalinized pattern has been described in endometrial endometrioid carcinoma. Herein, we describe a clinicopathological and molecular analysis of the first reported case of endometrial serous carcinoma with a corded and hyalinized pattern.A 64-year-old woman underwent hysterectomy and bilateral salpingo-oophorectomy due to a 5.5 cm endometrial lesion. Histologically, the tumor was composed of a minor (20%) serous carcinoma component and a predominant corded component embedded in a hyaline-to-myxoid matrix. This component showed diffuse and strong p53 and p16 expression, heterogeneous positivity for epithelial markers and WT1, focal positivity for estrogen and progesterone receptors, retained MMR, SMARCA4/BRG1, and SMARCB1/INI1 expression, and negativity for smooth muscle, germ cell, sex cord, neuroendocrine, endothelial, and melanocytic markers and GATA3. Next-generation sequencing showed a mutation of uncertain significance in APC and no mutations in MLH1, MSH2, MSH6, PMS2, MUTYH, POLE, POLD1, EPCAM, or CTNNB1. The patient had a recurrence on the vaginal stump after 15 months.In conclusion, endometrial serous carcinoma can show a corded and hyalinized pattern, which may represent a diagnostic challenge.

Pink-on-pink: hepatocellular carcinoma metastatic to oncocytic carcinoma of the thyroid.

Hepatocellular carcinoma typically metastasizes within the liver and may involve extrahepatic sites such as the lungs, adrenal glands, and bones at advanced stages. However, hepatocellular carcinoma metastasis to the thyroid is very uncommon and tumor-to-tumor metastasis from a hepatocellular cancer to a thyroid neoplasm is extremely rare. In this report, we present a case of a 70-year-old man with a hepatocellular carcinoma metastasizing to oncocytic thyroid carcinoma, emphasizing the importance of clinical history and of a multidisciplinary approach, as well as the usefulness of site-specific immunohistochemical markers, in diagnosing and managing cases of Rosai's metastasis, especially when donor and recipient neoplasms share similar histologic features.

The expression of intermediate filaments in the abomasum of ruminants: A comparative study.

Intermediate filaments (IFs) are key molecular factors of the cell and have been reported to play an important role in maintaining the structural integrity and functionality of the abomasum. This study was designed to determine the regional distribution, cellular localization and expression of several IFs, including CK8, CK18, CK19, vimentin, desmin, peripherin and nestin, as well as the connective tissue component laminin, in the bovine, ovine and caprine abomasa. Immunohistochemical analyses demonstrated varying levels of expression of CK8, CK18, CK19, vimentin, desmin, nestin, peripherin and laminin in the bovine, ovine and caprine abomasa. CK8 immunoreactions were particularly evident in the luminal and glandular epithelia of the glands found in the abomasal cardia, fundus and pylorus in all three species. In the bovine abomasum, CK18 immunoreactions were stronger in the parietal cells, compared to the chief cells. In the abomasum of all three species, the smooth muscle as well as the smooth muscle cells of the vascular media in the cardiac, fundic and pyloric regions showed strong immunoreactivity. In all three species, the cardiac, fundic and pyloric regions of the abomasum showed strong peripherin and nestin immunoreactions in the luminal and glandular epithelial cells, stromal and smooth muscle cells, nervous plexuses and blood vessels. The expression patterns of IFs and laminin in the ruminant abomasum suggest that these proteins play a structural role in the cytoskeleton and are effective in maintaining abomasal tissue integrity and stability.

Molecular alterations and prognosis of breast cancer with cutaneous metastasis.

PURPOSE: Cutaneous metastasis (CM) accounts for 5-30% of patients with breast cancer (BC) and presents unfavorable response to treatment and poor prognosis. A better understanding of the molecular alterations involved in metastasis is essential, which would help identify diagnostic and efficacy biomarkers for CM. MATERIALS: We retrospectively reviewed a total of 13 patients with histological or cytological diagnosis of breast cancer and CM. Clinical information was extracted from the medical records. The mutational landscape of matched primary tumors with their lymph nodes or CM tissues were analyzed using next-generation sequencing (NGS) of 425 cancer-relevant genes. All tissues were also analyzed by immunohistochemistry (IHC). The association of prognosis with various clinical and molecular factors was also evaluated. RESULTS: More than half of the patients were Ki67 low (< 50%, 53.7%). Most patients (12, 92.3%) had other metastasis sites other than skin. The median time from diagnosis to the presentation of CM (T1) was 15 months (range: 0-94 months) and the median time from CM to death (T2) was 13 months (range 1-78). The most frequently altered genes across the three types of tissues were TP53 (69.6%, 16/23), PIK3CA (34.8%, 8/23), and MYC (26.1%). The number of alterations in CM tends to be higher than in primary tumors (median 8 vs. 6, P = 0.077). Copy number loss in STK11, copy number gain in FGFR4, TERT, AR, FLT4 and VEGFA and mutations in ATRX, SRC, AMER1 and RAD51C were significantly enriched in CM (all P < 0.05). Ki67 high group (> 50%) showed significantly shorter T1 than the Ki67 low group (≤ 50%) (median 12.5 vs. 50.0 months, P = 0.036). TP53, PIK3CA mutations, and TERT amplification group were associated with inferior T2 (median 11 vs. 36 months, P = 0.065; 8 vs. 36 months, P = 0.013, 7 vs. 36 months, P = 0.003, respectively). All p values were not adjusted. CONCLUSION: We compared the genomic features of primary breast cancer tissues with their corresponding CM tissues and discussed potential genes and pathways that may contribute to the skin metastasis of advanced breast cancers patients. TP53, PIK3CA mutant, and TERT amplification may serve as biomarkers for poor prognosis for CM patients.

Mesonephric-type adenocarcinomas of the ovary: prevalence, diagnostic reproducibility, outcome, and value of PAX2.

Mesonephric-type (or -like) adenocarcinomas (MAs) of the ovary are an uncommon and aggressive histotype. They appear to arise through transdifferentiation from Müllerian lesions creating diagnostic challenges. Thus, we aimed to develop a histologic and immunohistochemical (IHC) approach to optimize the identification of MA over its histologic mimics, such as ovarian endometrioid carcinoma (EC). First, we screened 1,537 ovarian epithelial neoplasms with a four-marker IHC panel of GATA3, TTF1, ER, and PR followed by a morphological review of EC to identify MA in retrospective cohorts. Interobserver reproducibility for the distinction of MA versus EC was assessed in 66 cases initially without and subsequently with IHC information (four-marker panel). Expression of PAX2, CD10, and calretinin was evaluated separately, and survival analyses were performed. We identified 23 MAs from which 22 were among 385 cases initially reported as EC (5.7%) and 1 as clear cell carcinoma. The interobserver reproducibility increased from fair to substantial (κ = 0.376-0.727) with the integration of the four-marker IHC panel. PAX2 was the single most sensitive and specific marker to distinguish MA from EC and could be used as a first-line marker together with ER/PR and GATA3/TTF1. Patients with MA had significantly increased risk of earlier death from disease (hazard ratio = 3.08; 95% CI, 1.62-5.85; p < 0.0001) compared with patients with EC, when adjusted for age, stage, and p53 status. A diagnosis of MA has prognostic implications for stage I disease, and due to the subtlety of morphological features in some tumors, a low threshold for ancillary testing is recommended.

Immunohistochemical Diagnosis of Amyloid Typing: Utility and Limitations as Determined by Liquid Chromatography-Tandem Mass Spectrometry.

BACKGROUND: Although immunohistochemical techniques and proteomic analysis are widely used for typing diagnosis of amyloidosis, the diagnostic utility of immunohistochemical evaluation is not well understood. METHODS: We used immunohistochemical techniques to characterize staining patterns of in-house rabbit polyclonal anti-κ, anti-λ, anti-transthyretin antibodies, and commercial anti-amyloid A and anti-ß2-microglobulin antibodies in 40 autopsy cases. RESULTS: In thirty cases (75%), the subtype was determined by using the criterion that amyloid is strongly and diffusely positive for one antibody while negative for other antibodies. We then performed proteomic analysis of all 40 cases. In 39 cases, we identified only one amyloid protein and confirmed the immunohistochemically determined subtypes of the abovementioned 30 cases. In seven other cases, we could retrospectively determine subtypes with immunohistochemistry by using information from proteomic analysis, which increased the immunohistochemistry diagnosis rate to 92.5% (37/40). In one case, we identified double subtypes, both immunohistochemically and with proteomic analysis. In the remaining three cases, proteomic analysis was essential for typing diagnosis. CONCLUSIONS: The present findings suggest that combined immunohistochemistry and proteomic analysis is more useful than immunohistochemistry alone. Our findings highlight the importance of carefully interpreting immunohistochemistry for anti-TTR and light chain and offer insights that can guide amyloid typing through immunohistochemistry.