RNA-binding protein LIN28 is a marker for primary extragonadal germ cell tumors: an immunohistochemical study of 131 cases

Our plain-English summary of RNA-binding protein LIN28 is a marker for primary extragonadal germ cell tumors: an immunohistochemical study of 131 cases, by D. Cao, A. Liu, F. Wang, et al (Modern Pathology, 2011).

The study

• Authors: D. Cao, A. Liu, F. Wang, R.W. Allan, K. Mei, Y. Peng, J. Du, S. Guo, T.W. Abel, Z. Lane, J. Ma, M. Rodriguez, S. Akhi, N. Dehiya, J. Li
• Journal: Modern Pathology
• Published: 2011;24(2):288-96
• Cited by: 42 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

LIN28 has been shown to have an important role in primordial germ cell development and malignant transformation of germ cells in mouse. In this study, we examined the immunohistochemical profile of LIN28 in 131 primary human extragonadal germ cell tumors (central nervous system (CNS) 76, mediastinum 17, sacrococcygeal region 30, pelvis 3, vagina 2, liver 1, omentum 1, and retroperitoneum 1), including the following tumors and/or components: 57 seminomas/germinomas, 10 embryonal carcinomas, 74 yolk sac tumors, 6 choriocarcinomas, 15 mature, and 13 immature teratomas. We compared LIN28 with SALL4 to assess its diagnostic value. To determine its specificity, we examined LIN28 in 406 extragonadal-non-germ cell tumors (103 carcinomas, 91 sarcomas, 9 melanomas, 12 mesotheliomas, 83 lymphomas, 9 plasmacytomas, 82 CNS tumors, and 17 thymic epithelial tumors). The staining was semi-quantitatively scored as 0 (no cell stained), 1+ (0-30%), 2+ (31-60%), 3+ (61-90%), and 4+ (>90%). LIN28 staining was seen in all seminomas/germinomas (3+ in 1 and 4+ in 56), embryonal carcinomas (4+ in all 10), and yolk sac tumors (3+ in 3 and 4+ in 71). Variable LIN28 staining was seen in 5 of 6 choriocarcinomas (1+ to 4+), 8 of 13 immature teratomas (1+ to 2+ in immature elements), and in 1 of 15 mature teratomas (1+). Only 11 of 406 non-germ cell tumors showed 1+ LIN28 staining. Therefore, LIN28 is a sensitive (100% sensitivity) marker for primary extragonadal seminomas/germinomas, embryonal carcinomas, and yolk sac tumors with high specificity. Compared with SALL4, LIN28 demonstrated a similar level of diagnostic sensitivity for seminomas/germinomas and embryonal carcinomas. For primary extragonadal yolk sac tumors, although SALL4 stained all tumors (1+ in 1, 2+ in 2, 3+ in 10, and 4+ in 61), LIN28 stained more tumor cells (mean 95 vs 90%, P = 0.03) and was therefore more sensitive. For primary extragonadal yolk sac tumors, combining LIN28 and SALL4 can achieve a higher diagnostic sensitivity than either alone.

In plain English

This was a laboratory pathology study, not an asbestos exposure study. The authors stained 131 primary extragonadal germ cell tumors (germ cell tumors arising outside the testis or ovary) for the protein LIN28. They compared the results with previously reported staining for another marker, SALL4. LIN28 stained all 57 seminomas/germinomas. It stained over 90% of tumor cells in 10 of 10 embryonal carcinomas and 71 of 74 yolk sac tumors. In the yolk sac tumors, the average share of cells stained was 95% for LIN28 and 90% for SALL4. 73 of 74 showed staining in more than 90% of cells with one or both markers. Staining in choriocarcinomas and teratomas was variable. Among comparison tumors, 1 of 82 non-germ cell central nervous system tumors and none of 17 thymic epithelial tumors stained. Mesotheliomas appeared only in the authors' earlier comparison studies. The authors concluded that LIN28 can be used as a diagnostic marker for primary extragonadal seminomas/germinomas, embryonal carcinomas and yolk sac tumors, and more sensitive than SALL4 for yolk sac tumors. They noted that more non-germ cell tumors need study.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Immunohistochemical (tissue staining) study of tumor samples; laboratory pathology study
• Who was studied: 131 primary extragonadal germ cell tumors collected from the authors' institutions: 76 central nervous system, 17 mediastinum, 30 sacrococcygeal, 3 pelvis, 2 vagina, 1 retroperitoneum, 1 omentum, 1 liver. Comparison tumors were 82 primary non-germ cell central nervous system tumors and 17 thymic epithelial tumors. Dates of collection are not given.
• Exposure: No asbestos or other environmental exposure was studied. Tumors were stained with a LIN28 antibody, and the results were compared with previously reported SALL4 staining.
• Main results:
  • All 57 seminomas/germinomas showed positive staining for both LIN28 and SALL4.
  • Strong LIN28 staining in more than 90% of tumor cells was seen in 10 of 10 embryonal carcinomas and 71 of 74 yolk sac tumors.
  • In all 74 yolk sac tumors, the mean percentage of tumor cells stained was 95% for LIN28 and 90% for SALL4 (the article reports P = 0.03).
  • In 13 of 74 (18%) extragonadal yolk sac tumors, SALL4 stained fewer than 90% of tumor cells. These SALL4 results were previously reported.
  • 73 of 74 (99%) extragonadal yolk sac tumors showed staining in more than 90% of tumor cells with SALL4, LIN28, or both.
  • Among the 13 immature teratomas, 8 were positive for LIN28, and all 8 were also positive for SALL4.
  • 3 of 6 choriocarcinomas were positive for both LIN28 and SALL4. The article reports 2 more that were positive for LIN28 but negative for SALL4.
  • Only 1 of 82 primary non-germ cell tumors of the central nervous system stained for LIN28: a medulloblastoma, with weak staining in 1% of tumor cells.
  • None of the 17 thymic epithelial tumors showed LIN28 staining.
  • In the authors' earlier studies of 307 other extragonadal non-germ cell tumors, which included 12 mesotheliomas, only 10 showed weak LIN28 staining: 6 carcinomas, 1 sarcoma and 3 melanomas.
• The authors' conclusion: The authors concluded that LIN28 can be used as a diagnostic marker for primary extragonadal seminomas/germinomas, embryonal carcinomas and yolk sac tumors. They also concluded that it is more sensitive than SALL4 for primary extragonadal yolk sac tumors.
• Limitations the authors state:
  • The authors state that further studies including more extragonadal non-germ cell tumors are required.
  • The authors state that LIN28 staining does not distinguish a primary extragonadal germ cell tumor from one that has spread from elsewhere; clinical information is needed for that.

Topics

Medical terms in this study, explained in our Lexicon: Germ Cell Tumor, Malignant Transformation, Mediastinum, Omentum, Retroperitoneum, Carcinoma, Sarcoma, Mesothelioma.

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