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Case Reports: Monday, November 1, 2010 |

OCT3/4 Expression in a Primary Germ Cell Tumor of the Lung Leading to Cisplatin Resistance FREE TO VIEW

Shitij Arora, MD; Jagmeet Singh, MD; Sasikanth Nallagatla, MD; Jaime Cancel, MD; Harish Patel, MD; Pervez Mir, MD; Harinder Sawhney, MD; Afaf Abdu, MD
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Wyckoff Heights Medical Center, Brooklyn, NY



Chest. 2010;138(4_MeetingAbstracts):21A. doi:10.1378/chest.10721
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INTRODUCTION: Oct3/4 (POU5F1), a transcription factor essential for the maintenance of totipotency in embryonic stem cells, is expressed in germ cell tumors and has been labeled as the marker for primordial germ cells. Its interaction with the caudal-related homeobox gene (Cdx2) is responsible for the differentiation and maintenance of trophectoderm at the initial stages of development. Oct3/4 along with a transcriptional cofactor expressed in embryonic stem cells (Sox-2,Ch 3) are known to form a regulatory complex needed for the pluripotency of primitive embryonic stem cells. Extragonadal germ cell tumors are rare and it is even rarer to have the primary tumor located in the lung. We report a case of an Oct3/4 positive, Cdx2 negative germ cell tumor in the lung with no evidence of gonadal lesion. We also report the findings from in-situ hybridization studies that were done to analyze the chromosomal pattern of the tumor cells. We believe that this is the first report of such unique findings.

CASE PRESENTATION: A 48-year-old woman, chronic smoker, was admitted to our hospital with a dry cough and occasional hemoptysis for 3 months. On admission, the CT scan chest demonstrated three large soft tissue masses, the largest one being 12 x 10 cm. CT scan of the abdomen and pelvis was negative for involvement of any abdominal or pelvic organs. Pertinent labs included an alpha-fetoprotein (AFP) level of 254ng/ml, bHCG < 2 MIU/ml, alkaline phosphatase level of 131 units with intestinal isoenzyme level of 0%. The patient then underwent a left thoracotomy and left lobectomy for tissue diagnosis. Histochemical studies performed on resected specimen showed focal positivity for cytokeratin, alpha-fetoprotein, epithelial membrane antigen, and HCG. Placental alkaline phosphatase (PLAP), c-kit gene product (CD 117) , thyroid transcription factor-1 (TTF-1), Cdx-2, cytokeratin (CK) 7 and 20 were all negative. It was focally positive for Oct3/4 and strongly positive for the monoclonal antibody Ki-67. Cytogenetic analysis was performed using fluorescent in-situ hybridization technique. The most consistent result was the presence of Chromososme 3 polysomy seen in all the cells studied. The patient was put on Cisplatn and Etoposide and 6 month follow up showed increase in tumor size following which a second surgery was performed.

DISCUSSIONS: It appears that the tumor arose from primordial germ cells or embryonic stem cells because the tumor cells were positive, by immunostaining, for Oct3/4 and negative for CD34. Pelosi and colleagues in their reported case of a pure yolk sac tumor of the lung showed that the tumor had diffuse Cdx2 immunoreactivity [1]. Our case was completely negative for Cdx2 but showed diffuse Oct3/4 immunostaining. We hypothesize that the more differentiated form of this tumor may have some Cdx2 staining while Oct3/4 expression predominates for tumors that are more undifferentiated. Whether or not the degree of differentiation affects the response to chemotherapy is subject to further testing but studies have shown that Oct 3/4 expression confers resistance to platinum-based chemotherapy and more tumor invasion in bladder carcinoma. We also found, in our study of the cells, by FISH technique, consistent chromosome 3 polysomy. Whether this association is casual is to be evaluated by further studies.

CONCLUSION: We hypothesize that Oct3/4 is the marker for poorly differentiated germ cell tumors in the lung and confers resistance to Cisplatinum based chemotherapy regime. Also chromosome 3 polysomy may be playing a role through Sox-2 and Oct3/4 interaction in the development of the tumor.

DISCLOSURE: Jagmeet Singh, No Financial Disclosure Information; No Product/Research Disclosure Information

10:30 AM - 12:00 PM

References

PelosiG , Petrella, F, Sandri, MT, Spaggiari, L, Galetta, D, Viale, G.2006 Jul; A primary pure yolk sac tumor of the lung exhibiting CDX-2 immunoreactivity and increased serum levels of alkaline phosphatase intestinal isoenzyme.Int J Surg Pathol14,3247–5. [CrossRef]
 

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References

PelosiG , Petrella, F, Sandri, MT, Spaggiari, L, Galetta, D, Viale, G.2006 Jul; A primary pure yolk sac tumor of the lung exhibiting CDX-2 immunoreactivity and increased serum levels of alkaline phosphatase intestinal isoenzyme.Int J Surg Pathol14,3247–5. [CrossRef]
 
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