NKX3.1 Expression in Non-Prostatic Tumors and Characterizing its Expression in Esophageal/Gastroesophageal Adenocarcinoma.

The NKX3.1 immunohistochemical stain is widely recognized as a highly sensitive and specific marker for prostate adenocarcinoma. Nevertheless, its expression has been documented in various nonprostatic tissues and malignancies. This review aims to provide an overview of NKX3.1 expression in diverse tumor types, with a specific focus on its aberrant expression in esophageal/gastroesophageal adenocarcinoma (E/GE-ADC). In our investigation, we explored the expression of NKX3.1 in a series of E/GE-ADC to shed light on its prevalence in this tumor category. A total of 50 samples, comprising primary and metastatic E/GE-ADC specimens from 34 patients, were subjected to immunohistochemical analysis. Stained sections were scored based on the intensity and distribution-categorized as negative, weak, moderate, or strong in either a focal or diffuse pattern. Strong staining corresponds to the intensity observed in normal prostate controls, while focal and diffuse staining denote <50% and ≥50% of tumor nuclei staining positive, respectively. Our semiquantitative scoring revealed that 6 (12%) of the primary and metastatic E/GE-ADC specimens exhibited variable positivity for NKX3.1. This finding suggests that E/GE-ADC can sporadically stain positive for NKX3.1, introducing potential challenges in definitively determining the primary site of origin in certain clinical scenarios. Along with a literature review of NKX3.1 expression in other tumor types, our study provides additional important information about the extent to which this immunostain can be seen in E/GE-ADCs, which, to our knowledge, has not been reported.

The utility of the lineage specific immunohistochemical stains SATB2, CDX2, and villin, and the mucin glycoproteins MUC2, MUC5AC, and MUC6 to distinguish pulmonary invasive mucinous adenocarcinoma from metastatic colorectal carcinoma.

CONTEXT: The lungs are a common site of tumor metastasis. While morphology and immunophenotype can help differentiate primary from metastatic tumors, distinguishing pulmonary invasive mucinous adenocarcinoma (PIMA) from metastatic colorectal adenocarcinoma (CRC) may occasionally be challenging due to overlapping morphological and immunohistochemical features. Lineage-specific markers such as CDX2, TTF-1, and napsin A are helpful with pulmonary non-mucinous adenocarcinoma (PNMA), however they are non-specific and insensitive when applied to PIMA. SATB2 is a newer marker that distinguishes CRC from upper gastrointestinal and pancreaticobiliary tumors; its utility in distinguishing CRC from PIMA has not been fully elucidated. OBJECTIVE: To evaluate the performance of lineage-specific and mucin glycoprotein immunostains in distinguishing PIMA and CRC. DESIGN: We stained tissue microarrays comprising 34 PNMA, 31 PIMA, and 32 CRC with CK7, CK20, SATB2, CDX2, villin, TTF-1, napsin A, and gel-forming mucins MUC2, MUC5AC, and MUC6. RESULTS: PIMA showed significant (>50% of cells) expression of SATB2 (6%), CDX2 (6%), villin (74%), TTF-1 (13%), and napsin A (23%). However, significant CK7 expression was seen in nearly all PIMA (30/31) and none of the metastatic CRC. CONCLUSION: Our results suggest that CK7 remains one of the most useful markers for distinguishing primary PIMA from metastatic CRC. Expression of the mucin glycoproteins MUC5AC and MUC6 and lack of expression of MUC2 favored a diagnosis of PIMA, but expression of these markers was too heterogeneous to be of clinical utility. To our knowledge this is the only study comparing the immunohistochemical profile of PIMA and metastatic CRC in lung metastasectomy specimens.

Concurrent Down-Regulation of PTEN and NKX3.1 Expression in Iranian Patients with Prostate Cancer

ABSTRACT NKX3.1 and PTEN genes are involved in the development and progression of prostate cancer (PCa). Here, in line with other studies that correlated the expression of these two genes, we aimed at evaluating the expression pattern of these genes in clinical PCa samples. Collectively, 81 tissue samples including 45 human PCa and 36 benign prostatic hyperplasia (BPH) specimens were included in the study. The tissue samples were subjected to RNA extraction and subsequently to cDNA synthesis according to the kit manufacturer's protocol. Quantitative Real-Time PCR assay was performed for each sample in triplicate reactions. REST and SPSS software were used to statistically analyze PTEN and NKX3.1 gene expression data. Expression level of both NKX3.1 and PTEN genes was down-regulated in PCa samples compared to BPH samples. The relative expression ratio of PTEN and NKX3.1 was decreased to 0.155 and 0.003, respectively (P=0.000). The results of Chi-Square analysis revealed a significant correlation between the expression of these genes in both BPH and cancer groups (P=0.004 and 0.001, respectively). According to previous studies and our data, we concluded that the association between the down-regulation of PTEN and NKX3.1 genes contributed to the prostate tumorigenesis. This might highlight the interaction between the proteins encoded by these genes. Furthermore, this finding might be exploited for the development of innovative diagnostic and therapeutic approaches in PCa.

CDX-2, MUC-2 and B-catenin as intestinal markers in pure mucinous carcinoma of the breast

BACKGROUND: Pure mucinous adenocarcinoma of the breast is a rare entity characterized by the production of variable amounts of mucin comprising 1% to 6% of breast carcinomas. Some mucinous adenocarcinomas have shown expression of intestinal differentiation markers such as MUC-2. This study examines the expression of intestinal differentiation markers in this type of breast carcinoma. RESULTS: Twenty-two cases of pure mucinous adenocarcinoma of the breast were assessed. Immunochemistry was performed for beta-catenin, CDX-2 and MUC-2. All cases were positive for B-catenin. MUC-2 positivity was observed in all cases; 63. 6% were 3 plus positive. All cases were negative for CDX-2. CONCLUSIONS: These results suggest that mucinous breast carcinomas express some markers of intestinal differentiation, such as MUC-2 and beta-catenin; however, future studies with a larger series of cases and using molecular techniques that help affirm these results are needed.

The Usefulness of CDX-2 for Differentiating Primary and Metastatic Ovarian Carcinoma: An Immunohistochemical Study Using a Tissue Microarray

Distinguishing primary ovarian carcinoma from metastatic carcinoma to the ovary is often difficult by histologic examination alone. Recently an immunohistochemical marker CDX-2 was found to be of considerable diagnostic value in establishing the gastrointestinal origin of metastatic tumors. The aim of this study was to determine whether CDX-2 can distinguish between these malignancies. Paraffin-embedded tissue sections from 57 primary ovarian tumors and 40 metastatic tumors to the ovary were immunostained for CDX-2, and results were compared to the ancillary immunohistochemical results for CK7/CK20, CEA, CA125, and her-2/neu. CDX-2 immunoreactivity was observed in most of metastatic carcinomas with colorectal (91%) and appendiceal (100%) origin, however CDX-2 was negative in all primary ovarian carcinomas, except for the mucinous subtype. Almost all primary ovarian carcinomas including the mucinous subtype showed diffuse and strong immunoexpression for CK7. CEA and CA125 were mainly found in metastatic and primary ovarian carcinoma, respectively. Her-2/neu overexpression was only noted in a small proportion of primary and metastatic ovarian carcinomas. These results suggest that CDX-2 is very useful immunohistochemical marker for distinguishing metastatic colorectal carcinoma to the ovary from primary ovarian carcinoma, including the mucinous subtype. Furthermore, combination with CDX-2 and CK7 strengthen the differential diagnosis between these tumors.

Utility of Thyroid Transcription Factor-1 and Cytokeratin 20 in Identifying the Origin of Metastatic Carcinomas of Cervical Lymph Nodes

The identification of primary location of a metastatic tumor is a difficult diagnostic problem and sometimes can be facilitated by the use of immunohistochemical markers. Thyroid transcription factor-1 (TTF-1) is a 38-kDa nuclear homeodomain transcription factor that is expressed specifically in lung or thyroid neoplasms. Cytokeratin 20 (CK20) is a 46-kDa low-molecular-weight cytokeratin that shows restricted expression in adenocarcinomas of the gastrointestinal tract (GIT) and transitional cell carcinomas of the urinary tract. We studied the immunohistochemical expression of TTF-1 and CK20 in 68 metastatic carcinomas in cervical lymph nodes. The primary sites were the lung in 29 cases, stomach in 13, colorectum in 3, and other sites in 23. TTF-1 expression was detected in 69.0% of metastatic lung carcinomas and none in metastatic GIT carcinomas, whereas CK20 expression was detected in 68.8% of metastatic GIT carcinomas and none of metastatic lung carcinomas. TTF-1 had a specificity of 0.95 and a sensitivity of 0.69 for metastatic lung carcinoma, whereas CK20 had a specificity of 1.00 and a sensitivity of 0.69 for metastatic GIT carcinoma. These results indicate that TTF-1 and CK20 should be the first choice as a component of antibody panel to prove or to exclude the lung and GIT origin, respectively, especially in patients presenting with metastatic carcinomas of unknown primary site.