Cases Of Primary Lung Adenocarcinoma Research Articles

Sirt1 is a tumor promoter in lung adenocarcinoma.

Sirtuin 1 (Sirt1) is a nicotinamide adenine dinucleotide-dependent class III histone deacetylase. It reportedly can repress cellular apoptosis and senescence to affect DNA repair, stress response and aging. Notably, previous data have indicated that Sirt1 is both a tumor promoter and a tumor suppressor in tumorigenesis. However, Sirt1 expression in primary lung adenocarcinoma remains unknown. Immunohistochemical staining was performed to investigate Sirt1 expression in cancer cells in 125 consecutive resected cases of primary lung adenocarcinoma. Sirt1 expression was found to be increased in 26 (20.8%) of the 125 cases, which correlated significantly with five clinicopathological factors: Ki67 index, hypoxia-inducible factor 1 (HIF1) molecule expression, tumor-node-metastasis (TNM) classification, pulmonary vein invasion and lymphatic duct invasion. In the Sirt1-positive expression group, Sirt1 expression correlated with a higher Ki67 index and higher TNM classification, particularly for lymph node invasion and metastasis, and with a higher number of pulmonary vein invasion and lymphatic duct invasion. Additionally, a negative correlation was identified between HIF1-positive expression and Sirt1-negative expression. These results indicate that Sirt1 overexpression plays a promotional role in tumorigenesis and is closely associated with invasion and metastasis and, thus, it may be associated with prognosis.

A Columbus Tale - A Case of Primary Lung Adenocarcinoma With Unique Histochemical Features That Was Discovered During the Workup of a Suspicious Pelvic Mass

A Columbus Tale - A Case of Primary Lung Adenocarcinoma With Unique Histochemical Features That Was Discovered During the Workup of a Suspicious Pelvic Mass

Gastric and colonic metastases from primary lung adenocarcinoma: A case report and review of the literature

Lung cancer is one of the leading causes of cancer-related mortality worldwide. Gastrointestinal metastasis from primary lung cancer is rare. Only a few reports have been published and the majority of described metastatic sites involved the small intestine. In the present study, we report the first case of primary lung adenocarcinoma with both gastric and colonic metastases. We also review the published literature of primary lung cancer with gastrointestinal metastasis.

Napsin A is an independent prognostic factor in surgically resected adenocarcinoma of the lung

IntroductionNapsin A is regarded as a marker of lung adenocarcinoma. However, no comprehensive analyses of napsin A-positive lung ADCs or the prognostic significance of napsin A expression have been reported to date. Methods110 primary lung adenocarcinoma cases were analyzed for clinicopathologic parameters, including overall survival, stage, histology, napsin A and TTF-1 expression, EGFR mutation, and ALK rearrangement. ResultsNapsin A-positive adenocarcinomas were significantly more prevalent among tumors characterized as relatively small (p=0.023), non-solid predominant (p<0.001), non-mucinous/enteric (p<0.001), positive for TTF-1 expression (p<0.001), and positive for EGFR mutation (p=0.001). Multivariate analysis of overall survival demonstrated that the absence of napsin A was an independent prognostic factor for reduced survival time (p=0.002). ConclusionClinicopathologic characteristics associated with napsin A-positive lung ADC are similar to and overlap with those of TTF-1-positve ADCs. The absence of napsin A is an independent poor prognostic factor in surgically resected adenocarcinoma. Further studies are necessary to determine the role of napsin A in the progression of lung adenocarcinoma.

Lung cancer, thyroid cancer or both: An unusual case presentation.

Cancer metastasis to the thyroid is rare. Primary sites that have been reported to metastasize to the thyroid gland include breast and kidney. There are very few case reports describing metastasis of a lung primary cancer to the thyroid gland. We describe a case of a never-smoker patient with metastatic adenocarcinoma of the lung and a malignant thyroid mass presenting simultaneously. The thyroid biopsy could not distinguish whether it was a metastasis or incidentally found thyroid primary carcinoma. Based on EGFR mutational status it was determined that he has a primary lung cancer and thyroid metastasis. He was started on erlotinib and has had a marked response in both the lung and the thyroid masses. The presence of mutations within the EGFR gene can help distinguish lung adenocarcinoma from other carcinomas like thyroid cancer. This is the first published case of primary lung adenocarcinoma with metastasis to thyroid and with EGFR mutation.

Diagnostic utility of PAX8, TTF-1 and napsin A for discriminating metastatic carcinoma from primary adenocarcinoma of the lung

TTF-1 and napsin A are useful biomarkers for differentiating primary lung adenocarcinoma from metastatic tumors. Studies have shown, however, that TTF-1 and napsin A also can be expressed in extrapulmonary carcinomas, and that a small fraction of primary lung adenocarcinomas do not co-express these two markers. We attempted to determine whether a tissue-specific transcriptional factor, PAX8, can help determine primary sites of lung carcinomas. Immunohistochemical stains for PAX8, TTF-1 and napsin A were performed on 103 cases of metastatic lung carcinomas from a variety of origins and 120 cases of primary lung adenocarcinomas. Our data demonstrated that all 103 metastatic carcinomas were negative for napsin A, while 14 (13.6%; four thyroid, two endometrium, three colon, one prostate, one salivary adenoid cystic, two renal cell carcinomas, and one ovary) showed weak to strong TTF-1 nuclear staining in 5–60% of the tumor cells. All primary lung adenocarcinomas were negative for PAX8, whereas 46 (44.7%) metastatic carcinomas from the kidney (29/33), ovary (6/8), endometrium (5/5), endocervix (1/1), thyroid (4/5) and urinary tract (1/3) were positive for PAX8. Our data demonstrate that of combined use of PAX8, TTF-1 and napsin A is reliable to separate reliably lung primary from metastatic tumors.

Combination of Napsin A and TTF-1 Immunohistochemistry Helps in Differentiating Primary Lung Adenocarcinoma From Metastatic Carcinoma in the Lung

Differentiation of primary from metastatic adenocarcinoma in the lung can be challenging, and it demands sensitive and specific biomarkers, especially when the tissue for diagnosis is limited. Thyroid transcription factor-1 (TTF-1) has been considered a reliable marker for adenocarcinoma of lung origin. However, several recent studies have shown that TTF-1 immunostaining is also positive in adenocarcinomas arising in different organs including colon, endometrium, endocervix, and ovary. In addition, approximately 20% of lung primary adenocarcinomas are negative for TTF-1 immunostaining, and napsin A immunostaining has slightly higher sensitivity in detecting lung primary adenocarcinoma. We performed TTF-1 and napsin A immunostaining on 120 cases of primary lung adenocarcinomas and 37 cases of metastatic carcinomas in the lung. The results showed that 95 (79.2%) of 120 lung primary adenocarcinomas showed napsin A+/TTF-1+ double-positive immunostaining pattern. TTF-1⁻/napsin A+, TTF-1+/napsin A⁻, and TTF-1⁻/napsin A⁻ were seen in 8.3%, 3.3%, and 9.2% lung primary adenocarcinomas, respectively. Eight (21.6%) of the 37 metastatic carcinomas were positive for TTF-1 and they include clear-cell renal cell carcinomas completely negative for napsin A although napsin A was detected in 12 (80.0%) of 15 primary papillary and 3 (33.3%) of 9 primary clear-cell renal cell carcinomas. All renal epithelial neoplasms were TTF-1 negative. These findings indicate that double napsin A and TTF-1-positive immunostaining is highly specific for lung primary adenocarcinoma and the combination of these 2 biomarkers is warranted to help segregating primary lung adenocarcinoma from metastatic carcinoma in the lung.

淡明細胞腺癌優勢の肺原発混合型腺癌の１例―細胞診および病理組織学的観察―

淡明細胞腺癌優勢の肺原発混合型腺癌の１例―細胞診および病理組織学的観察―

Gross Cystic Disease Fluid Protein—(GCDFP-15)

A total of 211 cases of primary lung adenocarcinoma were tested for expression of gross cystic disease fluid protein-15 (GCDFP-15) and only 11 cases (5.2%) were positive. The cases occurred with an equal sex distribution in older individuals whose carcinomas were frequently identified on screening radiographs. The adenocarcinomas were peripheral lesions and had an average size of 2.9 cm (range, 1.1 to 7.0). Histologically, they were usually mixed acinar and papillary adenocarcinomas with abundant extracellular mucin production, with the neoplastic cells having a polygonal shape, round to oval nuclei, diffuse powdery chromatin, and abundant eosinophilic granular cytoplasm. Clear cells and apocrinelike cells with prominent central nucleoli were common. GCDFP-15 was expressed in conjunction with thyroid transcription factor-1 in 81% of cases and synaptophysin was seen in 65%. Estrogen and progesterone receptors were not expressed. EGFR gene amplification and mutations of exons 19 and 21 were rare. KRAS mutations and HER2 gene amplification were not seen. This report details the first 11 cases of pulmonary adenocarcinoma to express GCDFP-15 and their distinctive morphology with frequent mucin production and coexpression of thyroid transcription factor-1 and synaptophysin.

A Subset of Lung Adenocarcinomas and Atypical Adenomatous Hyperplasia–Associated Foci Are Genotypically Related

Atypical adenomatous hyperplasia (AAH) is considered the preinvasive lesion of pulmonary adenocarcinoma, and mutations of EGFR, HER2, and K-ras are involved in the early stage of lung adenocarcinoma carcinogenesis, also predicting clinical response to anti-EGFR small molecule inhibitors. We analyzed 18 cases of primary lung adenocarcinoma with concomitant AAH foci from 13 patients for mutations of EGFR (exons 18-21), HER2 (exons 19-20), and K-ras (exon 2) by direct sequencing polymerase chain reaction. Among mutated cases, concordant mutations of EGFR or K-ras in adenocarcinoma and related AAH were observed in 5 (63%) of 8 cases. In particular, 3 of 4 adenocarcinomas with EGFR mutations (all L858R point mutations in women, never or former smokers) had a concomitant and identical mutation in AAH, and 2 of 4 adenocarcinomas with K-ras mutations (both at codon 12 in women, a never and a current smoker) showed the same mutation in concomitant AAH. All cases were wild-type for HER2. Mutations of EGFR and K-ras genes represent an early event in lung adenocarcinomagenesis, and AAH convincingly seems to be a precursor lesion in a subset of cases of adenocarcinoma.

A rare case of primary lung adenocarcinoma detected by routine liquid-based cervical cytology

Cervical cytology is mainly used for the screening and detection of early cervical cancers and its precursors. Rarely, detection of malignant cells in cervical cytology specimens is the first manifestation of an extrauterine (EU) malignancy. We report a case of a 49-year-old female in which adenocarcinoma initially diagnosed on routine, liquid-based cervical cytology led to the detection of a primary lung cancer.

Prognostic impact of p53 protein overexpression in patients with node-negative lung adenocarcinoma

Prognostic value of p53 protein expression in node-negative lung adenocarcinoma is still controversy. The expression of p53 protein was examined immunohistochemically in lung adenocarcinoma using monoclonal antibody BP53-12. A total 131 cases of primary lung adenocarcinoma were examined. Relationship between expression of p53 protein and clinicopathologic factors were studied. Overexpression of p53 protein was found in 19 patients (14.5%). Univariate and multivariate analysis showed that overexpression of p53 protein was an independent prognostic factor in node-negative lung adenocarcinoma. p53 alteration could be a valuable predictor for prognosis in node-negative lung adenocarcinoma.

Possible mechanism of metastasis in lung adenocarcinomas with a micropapillary pattern

Micropapillary differentiation in adenocarcinomas has recently been associated with poor prognosis because these tumors are more likely to metastasize. However, no clear explanation exists as to why the presence of a micropapillary pattern is associated with metastasis. A case of primary lung adenocarcinoma with a prominent micropapillary pattern is presented here, with special reference to the immunohistochemical expression of the E-cadherin-mediated system and IQGAP1. Histologically, the tumor was diagnosed as a moderately differentiated papillary adenocarcinoma, showing an extensive micropapillary pattern, with intrapulmonary metastases, pulmonary disseminations, lymphovascular invasions, and lymph node metastases. Immunohistochemically, positive staining for the adhesion molecules E-cadherin, alpha-catenin, and beta-catenin was detected in both the micropapillary and non-micropapillary areas, whereas IQGAP1 was detected in the micropapillary, but not in the non-micropapillary, area. The adhesive function of E-cadherin depends on the integrity of the entire cadherin-catenin-actin network, and thus the expression of IQGAP1 may lead to adherens junction disassembly, and consequently, the release of carcinoma cells organizing in a micropapillary pattern. This is the first report to suggest correlation between adenocarcinoma with a micropapillary pattern and the presence of adhesion molecules, and offers an intriguing first glimpse on the role of the micropapillary pattern in the process of metastasis.

Cytology applications of p63 and TTF-1 immunostaining in differential diagnosis of lung cancers

The pathologic distinction of small cell from non-small cell-lung carcinoma is of considerable therapeutic significance. In particular, the ability to distinguish poorly differentiated non-small-cell lung cancer from small-cell lung carcinoma (SCLC) is at times difficult based upon morphology alone; available immunohistochemical markers such as neuroendocrine markers are of limited utility. We have demonstrated the role of p63 and thyroid transcription factor-1 (TTF-1) in the differential diagnosis of poorly differentiated squamous-cell carcinoma (PDSCC) versus SCLC, mostly in biopsy samples (Wu et al., American Journal of Clinical Pathology 2003;119:696-702). Here, we examine further the utility of this panel in cytologic cell-block samples of lung cancers including both primary and metastatic cancers of pulmonary origin, and cases of nonpulmonary cancers metastatic to lung in which differential diagnoses included a lung primary.Four-micron thick sections of 30 alcohol-fixed paraffin-embedded cell blocks from 14 lung FNAs, 6 liver FNAs, 3 bronchial washings, 1 subcarinal lymph node FNA, 1 iliac lymph node FNA, 1 pelvic mass FNA, 1 neck lymph node FNA, 1 adrenal FNA, and 1 pleural effusion were deparaffinized and stained with monoclonal antibodies reactive to p63 (1:800, Santa Cruz Biotechnology) and TTF-1 (1:50, Dako). Slides were stained for p63 using a streptavidin-biotin kit (BioGenex) and diaminobenzidine as chromagen, and counterstained with hematoxylin. Slides were stained for TTF-1 using a Dako Autostainer. Thirty cases were examined, including 8 primary SCLCs, 8 extra-pulmonary metastases of lung SCLCs, 4 PDSCCs and 4 primary pulmonary adenocarcinomas, and 6 nonpulmonary adenocarcinomas metastatic to lung or other sites. Fifteen out of 16 (94%) SCLC cases were p63-/TTF-1+, ranging in intensity from focal-weak to diffuse-strong; 1/16 SCLCs from a bronchial washing was p63-/TTF-1- but synaptophysin was positive. All 4 primary lung adenocarcinoma cases were p63-/TTF-1+; contrasting with nonpulmonary adenocarcinomas that were all p63-/TTF-1-. All 4 PDSCC cases were p63+/TTF-1-. The panel of p63 and TTF-1 appears to be useful in the diagnostic evaluation of cytologic cell-block samples of pulmonary malignancy.

Expression of Das-1 in Primary Lung Adenocarcinomas Represents Reactivation of an Oncofetal Pulmonary Antigen

Objective: The monoclonal antibody (mAb) designated as mAb Das-1 was generated against a colonic epithelial protein. It reacts with bronchiolar epithelium and submucosal glands and weakly with alveolar lining cells of fetal lung. Adult alveolar epithelium is, however, nonreactive for mAb Das-1. The present study was designed to evaluate the immunoexpression of Das-1 and to correlate it with the histomorphology of primary lung adenocarcinomas and intestinal metaplasia. Methods: Eighty-four cases of primary lung adenocarcinomas were reviewed and categorized according to histologic grade and subtype. Immunohistochemical staining with mAb Das-1 was performed with normal colon as control. Results: Expression of Das-1 in the submucosal bronchial glands also served as internal control. Strong and diffuse staining was seen in 33 of the 84 cases of adenocarcinomas (39%). Conclusions: Expression of Das-1 was seen in primary lung adenocarcinomas even though adult alveolar epithelium is negative. Staining with mAb Das-1 was seen regardless of the grade or histological subtype of the lung adenocarcinomas. As most primary lung adenocarcinomas are not of bronchial gland origin, expression of Das-1 represents activation of oncofetal antigens.

Micropapillary component in lung adenocarcinoma: a distinctive histologic feature with possible prognostic significance.

Micropapillary carcinoma or a micropapillary carcinoma component has been reported in the ovary, breast, and urinary bladder and is generally thought to have prognostic significance. However, little has been written on micropapillary differentiation in lung carcinoma. We studied 35 cases of primary lung adenocarcinoma with a micropapillary component seen at the M.D. Anderson Cancer Center. The micropapillary component in these tumors ranged from focal to prominent and was seen at both primary and metastatic sites. This component was not associated with any particular histologic subtype of lung adenocarcinoma. Of the 15 cases with available material, 14 (93%) stained positive for cytokeratin 7, whereas only two of the 15 cases (13%) stained positive for cytokeratin 20. Thyroid transcription factor-1 immunostaining of tumor nuclei was seen in 12 of the 15 cases (80%). Immunostaining was seen in areas both with and without micropapillary differentiation. Thirty-three of 35 patients (94%) developed metastases, which occurred most commonly in the lymph nodes (n = 26), and also in the lung (n = 17), brain (n = 9 cases), bone (n = 9 cases), and other sites. Most metastases had a prominent micropapillary component, irrespective of the extent of the micropapillary carcinoma component in the primary lung tumor. Adequate clinical follow-up information was available for 29 patients. The mean follow-up was 25 months. At their last follow-up, 16 of 29 patients (55%) were still alive with disease, 5 (17%) were dead of disease, and 8 (28%) were alive with no evidence of disease. We believe that a micropapillary component occurring in lung adenocarcinoma should be reported, as this component may be more likely to metastasize. The presence of this component should alert the clinician to search more carefully for metastases and have a closer follow-up on these patients. It is also important to recognize this component in evaluating a metastasis from an unknown primary site, as it should alert the pathologist to a possible primary in the lung in addition to breast, urinary bladder, and ovary.

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.

Cytologic Features Based on the Expression of E-cadherin and Catenins in Lung Adenocarcinoma

To investigate the relationship between E-cadherin-associated cell-to-cell adhesion and cytologic features in preoperative cytologic lung adenocarcinoma specimens. Evaluation of the relationship between cell-to-cell adhesion, formation of cellular clusters and frequency of single cells in 31 cases of primary lung adenocarcinoma, collected by brush and needle cytology preoperatively. Most cases with remarkable overlapping of cells in compact cellular clusters and a few solitary cells maintained cell-to-cell adhesion. Cellular clusters that had a slight tendency to overlap, a small cell-to-cell adhesion area and a high frequency of solitary cells tended to lack E-cadherin-associated cell-to-cell adhesion. Formation of cellular clusters and the appearance of solitary cancer cells are closely related to E-cadherin-associated cell-to-cell adhesion. Therefore, it is highly likely that cytologic features may indicate malignant behavior, such as local invasion and lymph node metastasis, in primary lung adenocarcinoma.

Relationship between TA01 and TA02 polypeptides associated with lung adenocarcinoma and histocytological features.

TA01 (molecular weight 35.0 kDa, isoelectric point 5.45) and TA02 (molecular weight 35.0 kDa, isoelectric point 5.29) polypeptides were detected using two-dimensional polyacrylamide gel electrophoresis (2-DE). A previous study has shown that these polypeptides are distributed in primary adenocarcinomas and some large-cell carcinomas of the lung. However, various expression levels of TA01 and TA02 polypeptides were demonstrated in adenocarcinoma, while large-cell carcinoma expressed low levels. To evaluate the relationship between the expression of TA01 and TA02 polypeptides and the histocytological features of primary adenocarcinoma of the lung, these two polypeptides were analysed by 2-DE combined with a non-enzymatic sample preparation technique, and their expression levels were compared with the histocytological features of primary lung adenocarcinoma. Out of 57 primary lung adenocarcinoma cases, 46 cases (80.7%) and 52 cases (91.2%) expressed TA01 and TA02 polypeptides respectively. Furthermore, the expression levels of TA01 and TA02 polypeptides correlated with the degree of cellular atypia, structural atypia and histocytological differentiation of primary lung adenocarcinoma. On the other hand, these two polypeptides were not detected in adenocarcinoma of the lung, metastatic from the colon and mammary glands. High expression of TA01 and TA02 polypeptides reflected the differentiation of primary adenocarcinoma in the lung. These two polypeptides are valuable in determining the histocytological differentiation of primary lung adenocarcinoma as well as in distinguishing between primary and metastatic adenocarcinoma of the lung.

Lung adenocarcinoma with type II pneumocyte characteristics

We report a case of primary lung adenocarcinoma with type II pneumocyte characteristics. Electron microscopic examination demonstrated that the tumour cells had well-developed microvilli and cytoplasmic lamellar inclusion bodies. These ultrastructural features are similar to those seen in type II pneumocytes of normal lung tissue. Western blot analysis, using monoclonal antibody against human surfactant protein A (SP-A), clearly demonstrated that the tumour cells expressed human SP-A, which is a major pulmonary surfactant protein produced by type II pneumocytes. These observations suggest that the tumour was derived from a type II pneumocyte.