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At least 19 recordsLinked to original sources
PubMed1996

The distribution and origin of keratin 20-containing taste buds in rat and human.

Sections of tissues containing lingual and extra-lingual taste buds were evaluated with monoclonal antibodies against cytokeratins. In the caudal third of the rat's tongue, keratin 20 immunoreactivity was restricted to taste buds, whereas keratins 7, 8, 18, and 19 were expressed in vallate and foliate taste buds and in cells of salivary ducts that merge with these taste epithelia. Hence, antibodies against keratin 20 most clearly distinguished differentiated taste cells from all other cells. In rat epiglottis, taste buds and isolated bipolar cells were keratin-20-positive. In rat nasopalatine papilla and palate, antibodies against keratin 20 identified Merkel cells, none of which was near to the keratin-20-negative taste buds. Nor were Merkel cells present at epiglottal taste buds or the keratin-20-negative fungiform taste buds or elsewhere in rat tongue. Hence, Merkel cells make no contribution to rat fungiform, epiglottal, nasopalatine, or palatal taste buds. Human and rat keratin-20-positive tissues are reported to be endodermal derivatives with the exception of Merkel cells and luminal urothelial cells. In rats the distribution of keratin-20-positive taste buds was in full agreement with the classical view that the posterior third of the tongue is derived from endoderm (keratin-20-positive taste buds), whereas the anterior two-thirds of the tongue is derived from stomadeal ectoderm (keratin-20-negative taste buds). The equally intense keratin 20 immunoreactivity of human fungiform and vallate taste buds violates this traditional rostro-caudal segregation and suggests that endodermally derived tissues may be present in the tip of the human tongue.

Adult↗
PubMed2001

Comparative analysis of tumor cell dissemination in mesenteric, central, and peripheral venous blood in patients with colorectal cancer.

BACKGROUND: Metastatic disease in colorectal cancer results from hematogenic dissemination of tumor cells. This dissemination can be explained by 2 concepts: (1) regional spread of tumor cells via portal venous drainage into the liver as the first site of metastasis and (2) early spread of tumor cells into central and peripheral venous blood as evidence of systemic hematogenic tumor cell dissemination. HYPOTHESIS: Tumor cell detection in different blood compartments could help to understand the predominant pattern of hematogenic tumor cell dissemination in colorectal cancer. DESIGN: Prospective consecutive series. SETTING: University hospital. PATIENTS AND METHODS: Mesenteric, central, and peripheral venous blood samples from 40 patients with colorectal cancer were examined by cytokeratin 20 reverse transcriptase polymerase chain reaction. MAIN OUTCOME MEASURES: Sensitivity and specificity of cytokeratin 20 reverse transcriptase polymerase chain reaction, and frequency of tumor cell detection in different blood compartments. RESULTS: Tumor cells were found in mesenteric venous blood of 20 of 40 patients, central venous blood of 6 of 40 patients, and peripheral venous blood of 2 of 19 patients. The detection rate in mesenteric venous blood was significantly higher than that in central and peripheral venous blood (P<.001). CONCLUSIONS: The significantly higher detection rate in mesenteric venous blood emphasizes the importance of the filter function of the liver for circulating tumor cells in portal venous blood. Tumor cell detection in central and peripheral venous blood, however, shows that this filtering process is limited and indicates early systemic hematogenic tumor cell dissemination in colorectal cancer.

Biomarkers, Tumor↗
PubMed1998

Spread of colorectal cancer micrometastases in regional lymph nodes by reverse transcriptase-polymerase chain reactions for carcinoembryonic antigen and cytokeratin 20.

BACKGROUND AND OBJECTIVES: Lymph node metastasis is known as a significant predictor of prognosis in colorectal cancer patients. Recently, reverse transcriptase polymerase chain reaction (RT-PCR) has been applied to detecting micrometastasis. To assess the risk of recurrence and accurately determine the spread of tumor cells, we examined lymph node micrometastases in a series of colorectal cancer patients. METHODS: We examined 202 lymph nodes obtained from 13 colorectal cancer patients who underwent curative operation and were histologically diagnosed to be node-negative, using RT-PCR to amplify mRNAs for two epithelial markers, carcinoembryonic antigen (CEA) and cytokeratin 20 (CK-20). RESULTS: All the cases, including early stage patients, had micrometastases. A total of 102 among 202 lymph nodes (50.5%) were positive for either CEA or CK-20, or both (47.0, 40.1, and 36.6% respectively). Positive lymph nodes were spread along the courses of vascular trunks as well as being located in more distant regions. CONCLUSIONS: Even in histologically negative lymph nodes, there is a considerable possibility that micrometastases may exist. Their detection by RT-PCR may improve clinical staging and indications for cancer therapy. We should also take care in the choice of surgical approach.

Adult↗
PubMed1999

Merkel cells in the human oesophagus.

Merkel cells (MCs) are well recognized in the basal layers of the skin and oral mucosa, but this paper describes for the first time the presence of MCs in the human oesophagus. These cells are not identified in neonatal oesophagus, but are seen singly and in clusters in adult specimens. Application of stereological techniques shows that MCs are more numerous in the mid-oesophageal region. Cells expressing established markers of MCs have also been demonstrated in two out of six primary small cell carcinomas of the oesophagus. Further investigation of the role of MCs in oesophageal innervation and epithelial biology will be of interest.

Adult↗
PubMed2000

Keratin 20 is a specific marker of submicroscopic lymph node metastases in colorectal cancer: validation by K-RAS mutations.

Lymph node status has major prognostic importance in colorectal cancer and greater precision in the diagnosis of lymph node metastases should provide better prognostic and therapeutic guidance. Keratin 20 (K20) gene expression has been used as a marker of lymph node metastases, but the evidence for this remains circumstantial. This study has therefore sought to determine K20 specificity and to correlate K20 expression with mutant K-RAS expression, in order to provide direct evidence that K20 expression in lymph nodes of colorectal cancer patients genuinely reflects metastatic disease. Specificity of K20 expression was established against a range of tissue types and 289 lymph nodes from 41 non-cancer control patients. K20 expression was restricted to gastrointestinal epithelia and was only present in one of the 289 control lymph nodes, giving a calculated specificity of 97.6% (95% confidence limits: 87.1-99.9%). Forty-two tumour samples were analysed for the presence of K-RAS codon 12 gene mutations using a RT-PCR mutant allele-specific amplification (MASA) technique. Thirteen tumours (31%) had codon 12 mutations detected by MASA and these were further analysed to determine the exact nature of the mutation. MASA was then used to screen the lymph nodes from these patients for the presence of the tumour-specific K-RAS transcript and the results were compared with K20 RT-PCR and histopathology from the same samples. Whilst K-RAS MASA was not as sensitive as K20 RT-PCR, there was substantial agreement between the assays. There were no K20-negative lymph nodes which were found to be K-RAS MASA-positive, whereas seven nodes in four patients were K20-positive and K-RAS-negative, in keeping with the differences in assay sensitivity. These results further validate K20 as a marker by providing greater certainty that what is being detected represents occult metastatic disease.

Biomarkers, Tumor↗
PubMed1999

Adenocarcinomas metastatic to the liver: the value of cytokeratins 20 and 7 in the search for unknown primary tumors.

BACKGROUND: Metastatic adenocarcinoma in the liver with an unidentified primary tumor site is a common clinical problem. Pathologists often are asked to identify the primary tumor site. The histologic picture itself usually is not helpful, because the histology may be similar in the metastases of tumors with different primary localizations. Immunohistochemistry can be helpful, but the previously recommended antibody panels are too complicated for everyday use. METHODS: A simple immunohistochemical algorithm with two monoclonal cytokeratin (CK) antibodies, CK20 and CK7, was tested on 93 autopsy cases of adenocarcinomas metastatic to the liver. Sections of the liver metastases were stained automatically and evaluated as negative (no staining), focally positive, or diffusely positive. Statistical comparison of the staining results for a single antibody was calculated as an odds ratio. RESULTS: Thirty-six of 93 (39%) metastases proved to be CK20 positive (+). In this group, the CK20+/CK7 negative (-) pattern was highly characteristic for colorectal localization of the primary tumor, having been observed 17 of 21 of the cases (81%). The CK20+/CK7+ pattern of the metastatic liver adenocarcinomas was highly suggestive of primary localization in the pancreas or biliary tract (11 of 14 cases; 79%). Exclusion of the tumors originating in the stomach raised these values to 94% and 92%, respectively. The statistically calculated predicted probability of primary tumor site being in the colon or rectum for CK20+/CK7- metastasis was 78,41%, the probability of a primary tumor being located in the pancreas or biliary tract was 74,85%, if calculated for the whole study group. CONCLUSIONS: The tested simple algorithm proved to be useful in CK20 positive (+) cases, predicting a primary tumor localization in the colon, rectum, pancreas, or biliary tract with high accuracy. The CK20- group was too heterogeneous to be classified adequately by these two antibodies.

Adenocarcinoma↗
PubMed1996

The detection of disseminated tumor cells in bone marrow from colorectal-cancer patients by a cytokeratin-20-specific nested reverse-transcriptase-polymerase-chain reaction is related to the stage of disease.

The dissemination of cancer cells is a prerequisite in the development of micrometastases and solid metastases. Our previous examinations of these cells were based on immunocytological staining of tumor-associated antigens and cytokeratins. We have now developed a highly sensitive and specific detection method based on a nested reverse-transcriptase-polymerase-chain reaction (RT-PCR) of cytokeratin-20 (CK-20) mRNA. Using this method, we examined the bone marrow of 57 patients with colorectal cancer and detected increasing numbers of CK-20-positive samples, depending on the UICC stage. Some 35% of all bone-marrow samples tested positive for CK-20: none were found in colorectal cancer stage 1, 24% were in stage II, 31% in stage III and 71% in stage IV. Investigation of bone-marrow specimens of patients with pancreatic cancer showed that 4 out of 11 patients were positive for CK-20 mRNA. To confirm that sample positivity for CK-20 expression was due to disseminated tumor cells, we examined bone marrow from a control group (n = 16) without apparent carcinoma. In this group, 15 out of 16 donors were CK-20-negative, while one donor with familial adenomatous polyposis showed a CK-20-specific signal.

Base Sequence↗
PubMed1998

Detection of colorectal cancer cells in peripheral blood by reverse-transcriptase polymerase chain reaction for cytokeratin 20.

The staging of colorectal cancer currently depends on pathological examination of the surgical specimen and regional lymph nodes, accompanied by imaging tests such as computed tomography (CT) scanning. However, alternative molecular methods to detect circulating tumour cells in blood or bone marrow may provide additional information about the extent of disease and prognosis. We have previously reported the development of a reverse-transcriptase polymerase chain reaction (RT-PCR) for cytokeratin 20 (CK 20) mRNA to detect circulating epithelial tumour cells. In this study, we report on the application of this method for detecting circulating tumour cells in patients with colorectal cancer. Using this method, CK 20 mRNA was detected in 8/8 human colorectal cancer cell lines, in 8/9 biopsies from primary colorectal tumours and in 9/10 biopsies of liver metastasis in patients with metastatic colorectal cancer, suggesting that CK 20 may be a useful target for the detection of circulating tumour cells in this patient group. In spiking experiments, 10 cells were consistently identified in 2 ml of whole blood (1 x 10(6)-1 x 10(7) mononuclear cells). In 12/25 (48%) peripheral blood samples from patients with known metastatic colorectal cancer, CK 20 mRNA was detected. However, there was no correlation between the detection of CK 20 mRNA in the peripheral blood and disease progression and survival in this group of patients. CK 20 mRNA was detected in 1/12 normal blood samples, which raises questions about the absolute specificity of CK 20 expression.

Adult↗
PubMed1996

Genotype/phenotype analyses of low frequency tumor cells using computerize image microscopy.

Techniques to identify low frequency (i.e., 10(-4)-10(-5)) tumor cells in bone marrow and peripheral blood of cancer patients provide opportunities for early detection of disseminated disease and characterization of the properties of cells released from the tumor. Low frequency epithelial cells in marrow and blood can be detected using immunophenotypic markers directed against intracellular and/or cell surface antigens. However, nonspecific phenotypic labeling may compromise the ability to discriminate tumor from nontumor cells. We describe optimization of slide-based approaches that facilitate identification and subsequent molecular cytogenetic characterization of rare tumor cell populations in hematopoietic tissues. Colon tumor cells seeded in a hematopoietic background provided a model system to optimize methodologies that are applicable to detection and quantification of micrometastases in clinical specimens. Mixtures of cytogenetically aberrant epithelial cells and hematopoietic cells on slides were labeled with an anti-cytokeratin 20 (anti-CK20) antibody that recognizes > 90% of colon adenocarcinomas. Computerized image analysis was used to record the location of the immunofluorescent cells on microscopic slides. Cells on slides were then hybridized using fluorescence in situ hybridization (FISH) with repeat-sequence DNA probes to detect aneusomies. Previously discriminated epithelial cells were relocated for molecular cytogenetic characterization. Tumor cells present at frequencies approximating 5 x 10(-5) were discriminated on the basis of immunofluorescence and cell size. A low frequency (4 x 10(-4)) population of normal hematopoietic cells also labeled with anti-CK20 (data not shown). This strategy of sequential immunophenotyping and molecular cytogenetic analyses may be useful to discriminate tumor from nontumor cells in cancer patients with micrometastatic disease.

Genotype↗
PubMed1997

Cytokeratins 20 and 7 in the differential diagnosis of metastatic carcinoma in cytologic specimens.

A series of 33 tumor cases (13 fine-needle aspirates and 20 effusion specimens) were evaluated for the expression of two cytokeratin (CK) subtypes; CK 20, expressed primarily in tumors of the GI tract, mucinous ovarian tumors and transitional cell carcinomas, and CK 7, found chiefly in non-GI tract adenocarcinomas, including breast and lung. CK 20 expression was demonstrated immunocytochemically in seven of seven metastatic colon and two of three metastatic transitional cell carcinomas tested. CK 20 was absent in all metastatic carcinomas of breast, ovary, lung, and uterus examined (23 cases). Anti-CK 7 stains were negative in four of six metastatic colonic carcinomas, with equivocal results in the remaining two cases. Metastatic lung, breast, and ovarian carcinomas were strongly positive for CK 7. This study demonstrates that the combined use of anti-CK 20 and anti-CK 7 antibodies is highly sensitive and specific for metastatic colonic adenocarcinoma in cytologic material and thus could play an important role in distinguishing this entity from other common primary carcinomas.

Antibodies, Monoclonal↗
PubMed1999

Utility of cytokeratin 7 and 20 subset analysis as an aid in the identification of primary site of origin of malignancy in cytologic specimens.

This study was undertaken to assess the utility of combined cytokeratin (CK) 7/20 immunoprofile determination in malignant cytologic cell blocks as an aid to the identification of tumor primary site of origin. Fifty-one cases in which CK 7/20 immunocytochemistry was performed as part of the initial workup were retrieved. Their contribution to the final cytologic diagnosis of tumor primary site of origin was analyzed. CK reactivity patterns were 7+/20- (n = 34), 7-/20+ (n = 9), 7-/20- (n = 7), and 7+/20+ (n = 1). The CK 7+/CK 20- immunophenotype was the most common one obtained, and due to its wide expression in a number of common carcinomas, the least informative. The second most common immunophenotype was CK 7-/20+, which is associated with colorectal origin, and as such was very useful when obtained. The CK immunoprofile was more useful in the setting of a prior carcinoma, being a major diagnostic determinant in 13 cases (55%) from group 1 (those with a prior history of malignancy), compared to 8 cases (29%) from group 2 (those with no prior history of malignancy). In the setting of prior carcinoma, the CK immunoprofile is most useful when carcinomas under consideration have different expected immunoprofiles (e.g., CK 7+/CK20- carcinomas, including lung, breast, ovary, endometrium, and others, vs. CK 7-/CK 20+ carcinomas, primarily colorectal). When similar immunoprofiles are obtained, their usefulness is greater if they are immunoprofiles other than the most common 7+/20- pattern. Similarly, in newly diagnosed carcinomas, the CK immunoprofile either helps to narrow the differential diagnosis or points to a specific diagnosis.

Biomarkers↗
PubMed2001

Genetic detection of lymph node micrometastases in patients with gastric carcinoma by multiple-marker reverse transcriptase-polymerase chain reaction assay.

BACKGROUND: Some patients with gastric carcinoma experience local disease recurrence despite undergoing curative resection of the tumor and regional lymph nodes (LNs), suggesting the presence of occult micrometastases. To evaluate the presence of gastric carcinoma micrometastasis in patients with otherwise histologically negative LNs, the authors established and tested a multiple-marker reverse transcriptase-polymerase chain reaction (RT-PCR) assay. METHODS: The authors assessed 435 LNs from 28 patients with gastric carcinoma who underwent gastrectomy with lymphadenectomy using the multiple-marker RT-PCR assay in addition to histologic examination. Carcinoembryonic antigen (CEA), cytokeratin-20 (CK-20), and MAGE-3 gene markers were used in this assay. LNs were scored positive for metastasis if at least one marker was positive. The presence of LN micrometastases also was verified by immunohistochemistry in histologically negative and RT-PCR positive LNs. RESULTS: Sixty-nine of 435 LNs (16%) were positive for CEA (12%), CK-20 (10%), or MAGE-3 (5%). None of 16 control LNs obtained from disease free patients was positive by RT-PCR assay. Of 414 histologically negative LNs, 50 LNs (12%) were scored as positive for metastasis by the assay. Of 26 patients who underwent curative resection, the disease stage was upgraded in 10 patients by genetic diagnosis (from Stage IA to Stage IB in 5 patients, from Stage IB to Stage IIIA in 2 patients, from Stage IB to Stage IV in 1 patient, from Stage IB to Stage II in 1 patient, and from Stage II to Stage IIIB in 1 patient). In the latter 10 patients, immunohistochemistry identified LN micrometastases in 4 patients. Two patients with micrometastasis by genetic diagnosis had recurrent disease within 1 year. CONCLUSIONS: The current results indicate that the multiple-marker RT-PCR assay is a useful tool for the detection of micrometastases in regional LNs in patients with gastric carcinoma and may improve the staging system of gastric carcinoma for these patients.

Adult↗
PubMed2001

The value of cytokeratins 20 and 7 in discriminating metastatic adenocarcinomas from pleural mesotheliomas.

BACKGROUND: Immunohistochemistry is a useful method in the differential diagnosis between pleural mesotheliomas and metastatic adenocarcinomas to the pleura. Cytokeratin (CK) 5-6 is one of the most specific mesothelioma-associated antibodies. Cytokeratin 20 and CK7 have been used successfully in studies determining primary location of adenocarcinomas from metastases. In the current study, the value of these CKs in differential diagnosis of malignant pleural lesions was examined. METHODS: Ninety-three autopsy-verified cases (14 mesotheliomas and 79 adenocarcinomas including 42 primary lung tumors and 37 adenocarcinomas metastatic to the pleura) were stained on CK20, CK7, and CK5-6 with commercially available primary antibodies. The staining was conducted in an automated immunohistochemical system. The results were analyzed statistically at different positivity thresholds: 10% and 0%. RESULTS: None of the mesotheliomas stained positively for CK20 at the 10% positivity level, but 3 cases showed focal positivity in < 10% of the tumor cells. Eighty-six percent (12 of 14) of these tumors were CK7+ and 64% (9 of 14) were CK5-6+. None of the mesotheliomas expressed the CK20+/7- pattern. Lung adenocarcinomas, both primary and metastatic, and breast carcinomas were very similar to mesotheliomas with regard to expression of CK20 and CK7 but differed significantly with regard to expression of CK5-6. Conversely, gastrointestinal adenocarcinomas and pancreaticobiliary tumors expressed CK20 positivity in a high proportion, 86% (13 of 15) and 77% (7 of 9), respectively. The gastrointestinal tumors stained positively for CK7 in only 20% (3 of 15) of cases and differed significantly from the other adenocarcinomas in this aspect. The CK20+/7- pattern was typical for gastrointestinal tumors. CONCLUSIONS: Adding CK20 and CK7 to the panel of antibodies in the differential diagnosis of pleural mesothelioma versus metastatic adenocarcinomas is useful because diffuse CK20 positivity seems to be an indicator of metastasis. Furthermore, CK7 negativity most often is associated with metastases, and the CK20+/7- pattern, typical of colorectal adenocarcinomas, is absent in pleural mesotheliomas.

Adenocarcinoma↗
PubMed2002

Cytokeratin expression patterns in noncardia, intestinal metaplasia-associated gastric adenocarcinoma: implication for the evaluation of intestinal metaplasia and tumors at the esophagogastric junction.

BACKGROUND: Barrett esophagus (BE)/Barrett adenocarcinoma and distal gastric intestinal metaplasia (IM)/adenocarcinoma are similar histologically, but they differ in their clinical presentation, epidemiology, and pathogenesis. Differentiating BE from gastric IM and Barrett adenocarcinoma from gastric adenocarcinoma is difficult, especially when IM is short or tumors are large and involve both sides of the esophagogastric junction. Previously, the authors identified unique cytokeratin (CK) immunoreactivity patterns that were associated strongly with BE and Barrett adenocarcinoma. The specificity of CK7 and CK20 (CK7/20) expression patterns in patients with IM-associated gastric adenocarcinoma, which is distinct epidemiologically from BE/Barrett adenocarcinoma, has not been evaluated. The objective of the current study was to evaluate the CK7/20 expression patterns in noncardia, IM-associated gastric adenocarcinoma in a Chinese population with a low risk for BE and esophageal adenocarcinoma and a high risk for Helicobacter pylori infection and gastric carcinoma. METHODS: Endoscopic biopsy specimens of gastric IM and adjacent tumor from 50 consecutive patients with advanced noncardia gastric carcinoma were immunostained for CK7 and CK20. Clinical and endoscopic features and H. pylori status were documented. Two gastrointestinal pathologists, blinded to clinical and endoscopic data, independently assessed CK7/20 immunohistochemistry. RESULTS: H. pylori infection was present in 43 of 50 patients (86%). In the area of IM, patchy CK7 staining was seen in 9 patients (18%), and diffuse CK20 staining was seen in all 50 patients (100%). The BE CK7/20 pattern characterized by CK7 staining in superficial and deep glands and the CK20 staining in surface epithelium was not seen in any of the 50 patients. Only one patient (2%) demonstrated a CK7 positive/CK20 negative immunophenotype characteristic of Barrett adenocarcinoma. The remaining 49 patients (98%) showed non-Barrett adenocarcinoma patterns of CK7/20 staining, i.e., a CK7 positive/CK20 positive pattern was seen in 33 patients (66%), a CK7 negative/CK20 positive pattern was seen in 12 patients (24%), and a CK7 negative/CK20 negative pattern was seen in 4 patients (8%). CONCLUSIONS: In a patient population without risk factors for the development of BE/esophageal adenocarcinoma, the CK7/20 pattern characteristic of BE was not present in gastric IM adjacent to adenocarcinoma, and the CK7/20 pattern characteristic of Barrett adenocarcinoma also was extremely rare. These results support the hypothesis that, despite the presence of intestinalized mucosa in both disorders, BE/Barrett adenocarcinoma and gastric IM/adenocarcinoma are two distinct clinical entities with unique demographic, clinical, and CK immunophenotypic findings. These results may have application to the evaluation of patients with IM and adenocarcinoma arising at the esophagogastric junction.

Adenocarcinoma↗
PubMed2001

Use of thyroid transcription factor 1, PE-10, and cytokeratins 7 and 20 in discriminating between primary lung carcinomas and metastatic lesions in fine-needle aspiration biopsy specimens.

BACKGROUND: The distinction of a primary lung carcinoma from a metastatic lesion is important, because the treatment and prognosis differ for patients with these malignancies. Such a distinction can be difficult because of overlapping cytologic features. It has been shown that antibodies to thyroid transcription factor 1 (TTF-1) and PE-10 are fairly specific markers for primary lung tumors in histologic specimens. TTF-1 regulates the expression of surfactant protein production, and PE-10 is a monoclonal antibody against components of human surfactant proteins. The combination of cytokeratin 7 (CK7) and cytokeratin 20 (CK20) immunoprofiling has been helpful in the identification of the primary site of origin of lung tumors. METHODS: In the current study, the authors evaluated the utility of TTF-1 and PE-10 immunostaining and also compared the staining with expression of CK7 and CK20 in the discrimination between primary lung tumors and metastatic lesions in 55 specimens from fine-needle aspiration (FNA) biopsies of the lung. Formalin fixed, paraffin embedded cell blocks from 35 primary lung tumors (16 adenocarcinomas, 8 squamous cell carcinomas, 6 large cell undifferentiated carcinomas, and 5 small cell carcinomas) and 20 metastatic carcinomas (6 breast lesions, 6 colon lesions, 3 urinary bladder lesions, 2 kidney lesions, 1 biliary tract lesion, 1 endometrial lesion, and 1 thyroid lesion) were immunostained with monoclonal antibodies to TTF-1, PE-10, CK7, and CK 20. Positive immunostaining for CK7, CK20, and PE-10 was based on cytoplasmic staining, whereas TTF-1 positive staining was based on nuclear staining of the neoplastic cells. RESULTS: Positive immunostaining with TTF-1 and PE-10 was noted in six primary lung tumors (17%). One metastatic lesion (5%) and two metastatic lesions (10%) were positive for TTF-1 and PE-10, respectively. The CK7 positive/CK20 negative immunophenotype was noted in 30 primary lung tumors (86%) and in 11 metastatic lesions (55%). The CK7 negative/CK20 negative immunophenotype was seen in four metastatic lesions and in the remaining five primary lung tumors. The CK7 negative/CK20 positive and CK7 positive/CK20 positive immunophenotypes were seen in two and three metastatic lesions, respectively, but in none of the primary lung tumors. When a CK7 positive/CK20 negative adenocarcinoma also demonstrated either TTF-1 positive or PE-10 positive staining, it was likely that the adenocarcinoma was of pulmonary origin (P < 0.035; Fisher exact test). The specificity of such a combination for discriminating between primary and metastatic adenocarcinomas was 94%. CONCLUSIONS: The results suggest that TTF-1, PE-10, or CK7/CK20 alone did not distinguish reliably between primary pulmonary tumors carcinomas and metastatic neoplasms of the lung in FNA biopsy specimens because of low sensitivity and specificity. The use of a panel of antibodies that includes CK7/CK20, TTF-1, and PE-10 may be helpful in discriminating between primary and metastatic adenocarcinomas of the lung. An adenocarcinoma is likely a primary lung tumor when it is of the CK7 positive/CK20 negative phenotype and demonstrates either TTF-1 positive or PE-10 positive staining.

Adenocarcinoma↗