Extrapulmonary Adenocarcinomas Research Articles

Utility of TTF-1 and Napsin-A in the work-up of malignant effusions.

Similar to TTF-1, Napsin-A is recently used increasingly to differentiate between pulmonary adenocarcinoma (P-ADC) and extra-pulmonary adenocarcinoma (EP-ADC). The aim of this study was to compare the performance of TTF-1 and Napsin-A in determining the primary origin of adenocarcinoma in malignant serous effusion. Following IRB approval, cellblocks from 139 cases of malignant serous effusions of histologically or clinically determined origin including: 26 P-ADC, 108 EP-ADC, 2 pulmonary squamous cell carcinoma (P-SQC), and 3 pulmonary small cell carcinoma (P-SCC) were retrieved. Each case was stained with Napsin-A and TTF-1 and evaluated for positivity and intensity of staining. Napsin-A and TTF-1 stained positive in 17/26 (65%) and 14/26 (54%) of P-ADC and in 2/108 (1.8%) and 0/108 (0%) of EP-ADC with a PPV of 89 and 100%, respectively. In combination, they positively stained 18/26 (70%) of P-ADC with a PPV of 90%. Out of 9 poorly differentiated P-ADC, 7 (78%) stained positive for Napsin-A, while 4 (45%) were reactive for TTF-1. Both Napsin-A and TTF-1 were negative in P-SQC, while P-SCC reacted positively for TTF-1 in 2/3 (66%) of cases and none for Napsin-A. Napsin-A and TTF-1 are both useful markers in distinguishing P-ADC from EP-ADC. However, Napsin-A performed better in poorly differentiated P-ADC and its mimickers. The nuclear staining of TTF-1 is crispier and much easier to interpret than Napsin-A cytoplasmic stain. An antibody panel including TTF-1 and Napsin-A or a dual stain will be very helpful in determining the origin of metastatic adenocarcinoma in serous effusion.

Trefoil factor 3 as a novel biomarker to distinguish between adenocarcinoma and squamous cell carcinoma.

In carcinoma, such as of the lung, the histological subtype is important to select an appropriate therapeutic strategy for patients. However, carcinomas with poor differentiation cannot always be distinguished on the basis of morphology alone nor on clinical findings. Hence, delineation of poorly differentiated adenocarcinoma and squamous cell carcinoma, the 2 most common epithelial-origin carcinomas, is pivotal for selection of optimum therapy. Herein, we explored the potential utility of trefoil factor 3 (TFF3) as a biomarker for primary lung adenocarcinoma and extrapulmonary adenocarcinomas derived from different organs. We observed that 90.9% of lung adenocarcinomas were TFF3-positive, whereas no expression of TFF3 was observed in squamous cell carcinomas. The subtype of lung carcinoma was confirmed by four established biomarkers, cytokeratin 7 and thyroid transcription factor 1 for adenocarcinoma and P63 and cytokeratin 5/6 for squamous cell carcinoma. Furthermore, expression of TFF3 mRNA was observed by quantitative PCR in all of 11 human lung adenocarcinoma cell lines and highly correlated with markers of the adenocarcinomatous lineage. In contrast, little or no expression of TFF3 was observed in 4 lung squamous cell carcinoma cell lines. By use of forced expression, or siRNA-mediated depletion of TFF3, we determined that TFF3 appeared to maintain rather than promote glandular differentiation of lung carcinoma cells. In addition, TFF3 expression was also determined in adenocarcinomas from colorectum, stomach, cervix, esophagus, and larynx. Among all these extrapulmonary carcinomas, 93.7% of adenocarcinomas exhibited TFF3 positivity, whereas only 2.9% of squamous cell carcinomas were TFF3-positive. Totally, 92.9% of both pulmonary and extrapulmonary adenocarcinomas exhibited TFF3 positivity, whereas only 1.5% of squamous cell carcinomas were TFF3-positive. In conclusion, TFF3 is preferentially expressed in adenocarcinoma and may function as an additional biomarker for distinguishing adenocarcinoma from squamous cell carcinoma.

Primary versus Metastatic Lung Adenocarcinoma in Patients with History of Extrapulmonary Adenocarcinoma: Incidence and Utility of Immunohistochemistry (IHC)

Primary versus Metastatic Lung Adenocarcinoma in Patients with History of Extrapulmonary Adenocarcinoma: Incidence and Utility of Immunohistochemistry (IHC)

Thyroid transcription factor-1 expression in colorectal adenocarcinomas

Although thyroid transcription factor-1 (TTF-1) immunoreactivity is considered as a specific marker of lung and thyroid neoplasms, it may be positive in a proportion of extrapulmonary adenocarcinomas. This study examined the expression of TTF-1 in 555 colorectal adenocarcinomas using three commercial monoclonal antibodies: clone SPT24 (Novocastra) and 8G7G3/1 (Dako and Cell Marque), and compared the TTF-1 staining with other immunohistochemical markers, cytokeratin (CK) 7, CK 20, caudal-type homeobox transcription factor 2 (CDX2), and MUC2. The clinicopathological prognostic factors were compared with the TTF-1 expression status. Nuclear TTF-1 staining was detected in 24 cases (4.3%) with the SPT24 antibody and 18 cases (3.2%) with the 8G7G3/1 antibody. All cases positive for 8G7G3/1 were also positive for SPT24. CDX2 was expressed constantly in all 24 TTF-1-positive colorectal cancers, whereas CK7, CK20, and MUC2 were detected in 2 (8.3%), 23 (95.8%), and 8 (33.3%) cases, respectively. There was no correlation between TTF-1 expression and clinicopathological significance. To avoid potential pitfalls, TTF-1 should be interpreted in conjunction with the clinical setting, histological features, and the results of other markers, such as CK7, CK20, and CDX2. MUC2 can be used as supplementary information to confirm difficult cases.

Tree-in-bud Pattern on Thoracic CT due to Pulmonary Intravascular Metastases From Pancreatic Adenocarcinoma

We report a case of pulmonary intravascular metastases from pancreatic adenocarcinoma manifesting as tree-in-bud pattern on thoracic computed tomography. Although infectious bronchiolitis is the most common cause of tree-in-bud pattern, this case emphasizes that the differential diagnoses include pulmonary intravascular metastases, particularly in patients with extrapulmonary adenocarcinomas.

Role Of TTF-1, CK20, And CK7 Immunohistochemistry for Diagnosis of Primary and Secondary Lung Adenocarcinoma

Thyroid transcription factor-1 (TTF-1), and cytokeratin 7 (CK7) and cytokeratin 20 (CK20) have recently been reported to be useful to distinguish between primary and metastatic lung adenocarcinoma. The aim of this study was to determine the usefulness of the staining patterns of pulmonary adenocarcinoma with antibodies to TTF-1, CK7, and CK20 in differentiating primary from metastatic pulmonary adenocarcinoma. Of the 66 lung adenocarcinoma specimens that were enrolled in our study, there were 40 primary lung adenocarcinomas, 12 metastatic adenocarcinomas from breast, 13 metastatic adenocarcinomas from colon, and 1 metastatic adenocarcinoma from stomach. The expression of TTF-1, CK7, and CK20 was assessed by immunohistochemistry. We found that 73% of primary lung adenocarcinomas expressed TTF-1, whereas all nonpulmonary adenocarcinomas lacked TTF-1 staining. CK7 expression was significantly more frequent in adenocarcinomas of pulmonary and breast origin than gastrointestinal (GI) origin (p < 0.001). In contrast, CK20 expression was significantly more prevalent in adenocarcinoma that originated in the GI tract than that of pulmonary or breast origin (p < 0.001). A combination of TTF-1+CK7+CK20- was highly significantly associated with primary adenocarcinoma of lung (vs GI tract, p < 0.001; vs breast, p < 0.001). A combination of TTF-1-CKCK20+ was highly significantly associated with adenocarcinoma of GI origin (vs lung, p < 0.001; vs breast, p < 0.001). Our study has confirmed that expression of CK7, CK20, and TTF-1 is a useful immunohistochemical marker for diagnosis of lung tumors and for differential diagnosis of primary pulmonary adenocarcinomas from extrapulmonary adenocarcinomas metastatic to the lung. Application of this panel of antibodies might be expected to increase the accuracy of diagnosis.

Thyroid transcription factor-1 is highly sensitive and specific in differentiating metastatic pulmonary from extrapulmonary adenocarcinoma in effusion fluid cytology specimens.

Thyroid transcription factor-1 (TTF-1) is a homeodomain-containing transcription factor selectively expressed in thyroid, lung and diencephalon. It has been shown to label pulmonary adenocarcinoma, thyroid tumors, and small cell carcinoma (pulmonary and extrapulmonary) with relatively high sensitivity and specificity. The usefulness of this immunostain in cytology specimens has not been thoroughly discussed in the literature. The authors evaluated 36 effusion cytology cases (17 pleural effusion, 18 ascitic fluid, and 1 pericardial effusion) diagnosed as metastatic adenocarcinoma and with cell blocks prepared from the file of Pamela Youde Nethersole Eastern Hospital, Hong Kong, during a three-year period from 1998 to early 2001. The clinical, radiologic, cytologic, and histologic (if any) findings were reviewed. A provisional diagnosis of the primary site was deduced for each of the 36 cases by clinical, radiologic, and/or histologic correlation. Immunohistochemical study was performed on the cell block sections of the effusion cytology specimens using mouse monoclonal antibody against TTF-1, after microwave heat-antigen retrieval. The results were correlated with the primary origin of the metastatic adenocarcinoma. Among the 17 cases of metastatic pulmonary adenocarcinoma, 15 cases showed nuclear staining for TTF-1 in most of the tumor cells (sensitivity, 88.2%). None of the 19 cases of metastatic extrapulmonary adenocarcinoma expressed TTF-1 (specificity, 100%). The current study validates TTF-1 as a highly sensitive and specific immunomarker for distinguishing between metastatic pulmonary and extrapulmonary adenocarcinoma in effusion cytology specimens, which are known to be associated with intrinsic artifact due to less than ideal cellular preservation.

Is TTF1 a good immunohistochemical marker to distinguish primary from metastatic lung adenocarcinomas?

To evaluate the immunohistochemical expression of thyroid transcription factor 1 (TTF1) in primary and metastatic pulmonary adenocarcinomas, and test the diagnostic accuracy of this antibody, two surgical pathologists independently evaluated 34 cases of adenocarcinomas in the lung without clinical data and tried to distinguish between primary and metastatic cases using histological criteria exclusively. Thirteen cases were primary in the lung and 21 were metastases of extrapulmonary adenocarcinomas: 6 from the endometrium, 4 from the ovary, 3 from the colon, 2 from the kidney, 2 from the breast, 2 from the liver and 1 from the prostate. Afterward, the immunoreactivity of TTF1 in these neoplasms was evaluated and correlated with morphological and clinical data. The two pathologists were able to diagnose only 5 out of 13 cases of primary lung adenocarcinomas (sensitivity of 38.46%) and also misdiagnosed two primary malignancies as metastases. After correlation with TTF1 data, the sensitivity increased to 61.53%. The specificity of TTF1 was 100%. In conclusion, TTF1 is a highly specific marker for primary lung adenocarcinomas, and should be included in a panel of antibodies for the differential diagnosis between primary and metastatic adenocarcinomas of the lung.

Surfactant protein gene expression in metastatic and micrometastatic pulmonary adenocarcinomas and other non-small cell lung carcinomas: Detection by reverse transcriptase-polymerase chain reaction

Reverse transcriptase (RT)-PCR with primers specific for surfactant protein A (SP-A), B (SP-B), C (SP-C), and D (SP-D) genes was applied to detect metastatic non-small cell lung carcinomas. Forty-one paratracheal and subcarinal lymph nodes obtained from 41 patients with non-small cell lung carcinomas, 11 lymph nodes from 11 patients with extrapulmonary adenocarcinomas, and eight control lymph nodes from patients without cancer were analyzed using RT-PCR. PCR products corresponding to SP-B gene products were found in all eight control lymph nodes, offering evidence of SP-B gene expression in cells of lymphatic tissue. SP-A, SP-C, and/or SP-D transcripts were detected in 11 (84.6%) of 13 lymph nodes with histologically identifiable metastases of pulmonary adenocarcinomas and in 10 (55.5%) of 18 lymph nodes that were tumor free on routine histological examination. These findings provide evidence of micrometastatic nodal involvement which remains undetectable by conventional light microscopy but can be evaluated by surfactant RT-PCR. Gene expression of SP-A and SP-C was restricted to metastatic pulmonary adenocarcinomas but SP-D gene activity has been also detected in two of four metastases of pulmonary large cell carcinomas, one adenosquamous carcinoma, and nine extrapulmonary adenocarcinomas as well.