Table 3 GRADE evaluation of literature for immunohistochemical markers that can be used to determine high risk of malignancy in GD
From: Association of immunohistochemical markers with premalignancy in Gonadal Dysgenesis
Quality assessment | Summary of findings | Quality | |||
|---|---|---|---|---|---|
Author | Study design and objective | Design limitations | Sample | Results/Conclusions | |
Inconsistency of results | |||||
Indirectness of evidence | |||||
Palma (2013) | Retrospective Observational Study | Insufficient sample size | 18 gonadal samples from 15 pediatric patients with 45,X/46,XY PGD | 1 patient had GB, 1 patient had DG | Low |
To determine whether OCT 3/4 and β-Catenin are expressed in dysgenetic gonads before GB development and whether TSPY participates in malignant invasive behavior | No inconsistencies | Ages not specified | 14/18 samples stained + for OCT 3/4 | ||
Head-to-Head comparison in correct population | Only 3 samples stained + for β-catenin | ||||
-Seen in Dysgenetic testes, UGT, GB, and DG, not + in streak tissue or mature germ cells | |||||
Tissue expressing OCT 3/4 and TSPY is associated with a high risk for GB development. | |||||
Suggest that β-catenin is not involved in dysgenetic gonad progression to GB, participates after GB is established. | |||||
Barros (2011) | Retrospective Observational Study | Insufficient sample size | 32 gonadal samples from 16 patients with Turner Syndrome and Y chromosome material | 19 % had + nuclear OCT4 staining, suggesting the presence of germ cell tumor cells (likely GB or CIS) | Low |
To investigate the frequency of gonadal tumors among patients with Turner syndrome and Y-chromosome material | No inconsistencies | Ages 8–18 yrs. | OCT4 immunohistochemistry is more sensitive than conventional H&E staining to indicate the risk of development of germ cell tumors in TS patients | ||
Head-to-Head comparison in correct population | |||||
Palma (2008) | Retrospective Observational Study | Insufficient sample size | 7 patients with PGD and GB | OCT 3/4 was + in the nuclei of immature germ cells in GB | Low |
To evaluate the participation of β-catenin and OCT 3/4 in the oncogenic pathways involved in the transformation of GB into seminoma/DG | No inconsistencies | Ages 2–33 m | Β-catenin was overexpressed in immature germ cells in GB | ||
Head-to-Head comparison in correct population | Β-catenin and OCT 3/4 co-localized in immature germ cells in GB nests in all cases | ||||
The proliferation of immature germ cells in GB may be due to an interaction between OCT 3/4 and accumulated β-Catenin in the nuclei of the immature germ cells | |||||
Cools (2006) | Retrospective Observational Study | Insufficient sample size | 60 gonadal samples from 43 patients with GD | Incidence of GCTs was 35 % | Low |
To define the histological origin of GB, allowing the identification of high-risk patients | No inconsistencies | Ages 1 m-25 yrs. | Germ cells within GB were + for OCT 3/4, c-KIT, PLAP, and TSPY | ||
Head-to-Head comparison in correct population | In UGT found adjacent to GB, OCT 3/4, PLAP, and c-KIT + germ cells were found | ||||
A gonadal biopsy revealing the presence of UGT with OCT 3/4 + cells on the basal lamina contains high risk for GCT and should lead to gonadectomy. | |||||
Quality assessment | Summary of findings | Quality | |||
Author | Study design and objective | Design limitations | Sample | Results/Conclusions | |
Inconsistency of Results | |||||
Indirectness of Evidence | |||||
Cools (2005) | Retrospective Observational Study | Insufficient sample size | 58 gonadal samples from 30 patients with undervirilization syndromes | OCT 3/4 was found in all patients <9 m of age | Low |
To distinguish germ cells with maturation delay from those with CIS | Different populations (not looking specifically at GD patients) | Ages 1 m-23 yrs. | -In young patients and controls, OCT 3/4 + cells were found centrally in the tubule | ||
-In 3 older patients with CIS, OCT 3/4 + cells were found along the basal lamina | |||||
Expression of PLAP and c-KIT was similar to OCT 3/4, but less consistent | |||||
The presence of germ cells + for OCT 3/4, PLAP, or c-KIT in patients < 1 yr is in accordance with expected maturation delay and is insufficient for the diagnosis of CIS. | |||||
The location of OCT 3/4 positive cells is important in differentiating between CIS and maturation delay | |||||
Kersemaekers (2005) | Retrospective Observational Study | Insufficient sample size | 6 gonads from 5 patients with GD containing GB | 4 patients had DG arising from GB | Low |
To investigate the pathogenesis of GB and evaluate its relationship to CIS. | No inconsistencies | ||||
Head-to-Head comparison in correct population | Ages 14–21 yrs. | c-KIT was the least consistent marker | |||
PLAP was + in all GBs and adjacent invasive components. | |||||
Most of the tumor cells in invasive DG were weakly + or - for PLAP. | |||||
OCT 3/4 was + in all GBs and DGs | |||||
Seen in more immature cells, not mature cells | |||||
The development of an invasive germ cell tumor seems to involve selection and clonal expansion of an immature germ cell + for OCT 3/4 and TSPY | |||||
Slowikowska-Hilczer (2001) | Retrospective Observational Study | Insufficient sample size | 23 patients with XY GD | On the basis of PLAP expression, CIS was detected in 10 cases (43.5 %) with GD. | Low |
Ages 3 m-7 yrs. | GB was found in 4 cases of GD and DG was found in 1 patient with GD (17 years old) | ||||
No inconsistencies | |||||
To investigate the appearance of CIS in patients with 46,XY testicular dysgenesis in different ages and in adult patients from other groups | |||||
Head-to-Head comparison in correct population | |||||
Results showed a high prevalence of CIS in XY GD, indicating the importance of early histopathological evaluation of the gonads in these patients | |||||