|Year : 2022 | Volume
| Issue : 4 | Page : 814-820
|Diagnostic and prognostic utility of SF-1 in adrenal cortical tumours
Priyanka Maity1, Akash Mondal1, Rhituparna Das1, Moumita Sengupta1, Piyas Gargari2, Anish Kar2, Debansu Sarkar3, Satinath Mukhopadhyay2, Subhankar Chowdhury2, Uttara Chatterjee1
1 Department of Pathology, IPGME&R, Kolkata, India
2 Department of Endocrinology, IPGME&R, Kolkata, India
3 Department of Urology, IPGME&R, Kolkata, India
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|Date of Submission||10-Feb-2021|
|Date of Acceptance||15-Mar-2021|
|Date of Web Publication||06-Jun-2022|
| Abstract|| |
Background and Aims: Superior imaging techniques have increased the recognition of adrenal pathology. Distinguishing benign from malignant adrenocortical tumors is not always easy. Several criteria and immunohistochemical markers have been discovered which help to differentiate between adrenocortical adenoma (ACA) and adrenocortical carcinoma (ACC). Our aim here was to evaluate the diagnostic and prognostic role of steroidogenic factor-1 (SF-1) in adult adrenocortical tumors (ACT) diagnosed using the Weiss criteria. In this cohort, we have also analyzed Ki67 and p53 expression and the extent of agreement between SF-1 and Ki-67. Methodology: This was a retrospective, observational study comprising 24 cases of adult ACT over 10 years. Immunohistochemical staining for SF-1, Ki67, and p53 was done in all the cases, and the results correlated with the morphological diagnosis made using Weiss criteria. Results: SF-1 was 100% sensitive and 80% specific as a marker of malignancy. Increased SF-1 expression correlated with worse survival. There was a moderate degree of agreement between Ki-67 labeling-index and SF-1 as a marker of malignancy with the kappa coefficient being 0.75. The sensitivity of p53 was lower than Ki67 in diagnosing ACC. Conclusion: In adult ACTs, SF-1 has diagnostic significance and prognostic implication. SF-1 is a crucial, dosage-dependent survival factor in ACC. There is a moderate extent of agreement between Ki-67 and SF-1 as a marker of malignancy.
Keywords: Adrenocortical tumors, Ki-67, p53, steroidogenic factor-1, Weiss criteria
|How to cite this article:|
Maity P, Mondal A, Das R, Sengupta M, Gargari P, Kar A, Sarkar D, Mukhopadhyay S, Chowdhury S, Chatterjee U. Diagnostic and prognostic utility of SF-1 in adrenal cortical tumours. Indian J Pathol Microbiol 2022;65:814-20
|How to cite this URL:|
Maity P, Mondal A, Das R, Sengupta M, Gargari P, Kar A, Sarkar D, Mukhopadhyay S, Chowdhury S, Chatterjee U. Diagnostic and prognostic utility of SF-1 in adrenal cortical tumours. Indian J Pathol Microbiol [serial online] 2022 [cited 2022 Dec 7];65:814-20. Available from: https://www.ijpmonline.org/text.asp?2022/65/4/814/346684
| Introduction|| |
Adrenal pathology is increasingly being recognized with the widespread use of superior imaging techniques. These are often referred to as incidentalomas, meaning clinically and hormonally asymptomatic lesions detected by chance during imaging. The reported prevalence of incidentalomas is around 3% in middle age and 10% in the elderly. Most of these incidentalomas are small, nonsecretory, and turn out to be adenomas. A total of 5%–15% incidentalomas are hormonally active and are rarely due to metastatic deposit from a silent primary.
Similar to other endocrine neoplasms, in the adrenal gland too, it is difficult to differentiate benign from malignant tumors. Several criteria have been proposed to differentiate between ACA and ACC in adults, of which Weiss criteria is the most accepted one.,, Nevertheless, due to histological heterogeneity, it is not uncommon to come across cases where it is challenging not only to distinguish ACA from ACC but also from pheochromocytoma and metastasis. This differentiation is essential for management. Moreover, Weiss criteria are not always useful for the oncocytic variant, sarcomatoid variant, and myxoid variant of ACC and pediatric ACTs.
Numerous immunohistochemical markers have come up that confirms the adrenal origin of the tumor e.g., D11, Melan A, and α- inhibin. However, because of limited sensitivity, their usage has not been popular. ,, Steroidogenic factor 1 (SF-1), a nuclear transcription factor expressed in the nontumorous adrenal cortex as well as ACTs, has emerged as the most reliable marker for confirmation of adrenal cortical origin.,, It is expressed by a few other steroidogenic tissues only such as the ovary, testis, and pituitary. In ACTs, chromosomal gain in 9q, at the location of the SF-1 gene has been reported which suggests that gene amplification may be the basis of SF-1 overexpression in ACTs.
In addition to diagnostic utility, SF-1 has a potential role as a prognostic marker in ACCs. On immunohistochemistry (IHC), higher expression of SF-1 has been found to be associated with poor prognosis., We have earlier studied the diagnostic and prognostic utility of SF-1 in pediatric ACTs.,,,
In this study, we have evaluated the adult ACTs we came across in our daily practice. We have categorized them into ACA and ACC using Weiss criteria. Our study aims to evaluate SF-1, as a diagnostic marker in differentiating between ACA and ACC as well as a prognostic marker in ACC. In this cohort, we have also looked for Ki67 and p53 expression and the extent of agreement between SF-1 and KI67.
| Materials and Methods|| |
This was a retrospective, observational study comprising 24 cases of adult ACT over the last 10 years from June 2010 to May 2019. Patients with metastasis in the adrenal cortex or adrenal medullary neoplasms like pheochromocytoma were excluded from the study. The study was approved by the Institutional Ethical Committee. Clinical parameters about the cases such as age, sex, signs, and symptoms as well as relevant history were recorded. Patients with recurrent or metastatic disease were considered clinically malignant. Radiological findings along with operative findings were recorded.
Gross examination of the specimen was done including tumor weight and size after which sections were taken and processed for microscopic examination. The sections were carefully examined for architecture, clear cells, nuclear grade (Fuhrman), mitotic rate, atypical mitosis, necrosis, vascular invasion, sinusoid invasion, and capsular invasion. The final diagnosis was in accordance with the Weiss criteria, which required the presence of three or more than three of the following features for a diagnosis of ACC; high nuclear grade, >5 mitoses/50 HPF, abnormal mitosis, <25% clear cells, >33% diffuse architecture, tumor necrosis, vascular invasion, sinusoid invasion, and capsular invasion.
Immunohistochemistry was performed on formalin-fixed and paraffin-embedded tissue sections using SF-1, Ki67, and p53 antibodies. The following antibodies were used: anti-human SF-1 antibody (1:100 dilution; PerseusProteomics, Tokyo, Japan), anti-human Ki67 antibody (1:50 dilution; Dako, Denmark A/S), and anti-human p53 antibody (ready to use antibody). Negative and positive controls were prepared for each marker.
SF-1 expression was qualitatively graded into a three-tier system: 1 + when nuclear positivity was seen in less than 50% of the tumor; 2 + when 50% or more but less than 80% of the tumor section showed positivity for the marker; 3 + when nuclear positivity was seen in 80% or more of the tumor section. For the purpose of statistical analysis, we reported cases with a score of 1 + as negative, and 2 + and 3 + as positive.
The Ki67 labeling index (KI67 LI) was evaluated by counting Ki67 positive cells in five high-power fields (400x). Then, the percentage of positive cells in each of those five fields was calculated. Ki67 LI was expressed as the mean of percentages of those five fields. Ki67 proliferating index was considered as high if > 5% tumor cell nuclei were stained., Nuclear staining for p53 was considered positive if >5% of tumor nuclei showed positivity. The patients were followed up for a period of 4 to 60 months.
Numerical variables were compared between the ACA group and ACC group using Student's unpaired t-test, and categorical variables were compared between groups using Fischer's exact test 2 tailed. For each immunohistochemical marker, the standard diagnostic indices were calculated, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The extent of agreement between KI-67 and SF-1 as a marker of malignancy was calculated by using the kappa coefficient. A receiver operator characteristic (ROC) curve analysis was done to identify the cut-off for SF-1 percentage value for predicting mortality. Kaplan-Meier survival analysis was performed for comparing survival experience between SF-1 positive and SF-1 negative cases. All statistical analyses were done using Statistica version 6 [Tulsa, Oklahoma: StatSoft Inc., 2001] and MedCalc version 11.6 [Mariakerke, Belgium: MedCalc Software 2011]. P value of <0.05 was considered to be statistically significant.
| Results|| |
Twenty-four cases of adult ACTs were diagnosed over a period of 10 years with 15 ACAs and 9 ACCs. The mean age of patients with ACTs was 41 years (range: 20–57 years). The mean age of patients with ACA and ACC was 40 years (range: 20–55 years) and 42 years (range: 27–57 years), respectively, the difference between the two not being significant. The male-to-female ratio was 1:1.1 and 1:2 in ACA and ACC, respectively.
The ACTs were functional in fourteen cases and nonfunctional in ten cases. The functional cases consisted of nine ACAs and five ACCs, whereas the remaining nonfunctional cases consisted of six ACAs and four ACCs. The most common presentation of ACTs was Cushing syndrome (29.1%). The ACT was an incidental finding on imaging in 20.8% of cases. This was followed by abdominal discomfort (12.5%), virilization (12.5%), abdominal mass (8.3%), flank pain (8.3%), and hyperaldosteronism (8.3%). The functional tumors presented with Cushing syndrome, hyperaldosteronism, virilization, or hypertension while the nonfunctional tumors presented as incidentalomas detected on imaging or with abdominal mass, abdominal discomfort, or flank pain.
The range of weight of ACTs was from 25 to 1100 g with a mean of 331 g. The mean tumor weight of ACAs was 117 g (range: 25300 g), whereas in ACCs the mean tumor weight was significantly higher, 688 g (range: 450–1100 g). The range of size of ACT was from 2.5 cm to 15 cm with a mean of 6.7 cm. The ACAs had an average size of 4.7 cm (range: 2.5 cm–10 cm), wereas the average size for ACCs was 10.1 cm (range: 7 cm–15 cm). Extra-adrenal extension was present in four out of nine ACCs, whereas it was absent in all the ACAs.
Using Weiss criteria, 15 cases were classified as ACA and 9 cases as ACC. Out of nine ACCs, seven (77.8%) showed >33% of diffuse architecture, but it was absent in all the fifteen ACAs. Clear cytoplasm covering less than 25% of the area in histological sections was seen in seven ACCs (77.8%), whereas it was lacking in all the ACAs. Six cases of ACCs (66.7%) and none of the ACAs had involvement of the margins. The difference in the number of cases with >33% of diffuse architecture, less than 25% of clear cytoplasm, and margins positive for tumor between the ACC and ACA group were significant.
In ACAs, the mean mitotic rate per 50 high power fields was 5 (range: 4–10), whereas in ACCs it was significantly higher, with a mean of 16 (range: 6–28). High nuclear grade (grade 3 and grade 4) was noted in all the ACCs (100%) and only one ACA (6.7%). Out of nine ACCs, two had a nuclear grade of 4, whereas seven had a nuclear grade of 3. Out of fifteen ACAs, there were three, five, and seven cases of nuclear grades 3, 2, and 1, respectively. Evidence of atypical mitoses was noted in eight ACCs (88.9%), whereas it was seen in only one ACA (6.7%). Tumor necrosis was not evident in any of the ACAs, whereas it was present in all of the ACCs (100%). There was a significant difference in expression of nuclear grade, atypical mitotic figures, and necrosis between the ACC and ACA groups. No association was detected between the two groups and tumor laterality.
On microscopic examination, the vascular invasion was observed in five out of nine ACCs. These five cases also showed sinusoidal invasion. The capsular invasion was seen in seven ACCs. None of the ACAs showed vascular or capsular invasion. A comparison of the histopathological variables between ACA and ACC is summarized in [Table 1].
|Table 1: Comparison of the histopathological variables of Weiss criteria between ACA and ACC|
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SF-1 was positive in all ACCs (100%), with a grade of 3 in each case, whereas it was positive in three ACAs (20%), with a grade of 2 and negative in twelve ACAs (80%), with a grade of 1. SF-1 positivity was analyzed to have: 100% sensitivity, 80% specificity 75% PPV, and 100% NPV as a marker of malignancy. In ACAs, the mean SF-1% was 34.8% (range: 15%–60%), whereas in ACCs the mean SF-1% was significantly high at 87.1 (range: 78%–95%) [Figure 1]. An ROC curve analysis identified the cut-off for SF-1 percentage value for predicting mortality to be 82%. A Kaplan-Meier survival analysis performed for comparing survival experience between SF-1 positive and SF-1 negative cases revealed that increased SF-1 expression correlated with worse survival. (P: 0.009) [Figure 2] and [Figure 3].
|Figure 2: ROC curve analysis identifying the cut-off for SF-1 percentage value for predicting mortality to be 82%|
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|Figure 3: Kaplan-Meier survival analysis, comparing survival experience between SF-1 positive and SF-1 negative cases, showing increase SF-1 expression correlates with worse survival|
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Ki 67 was positive (≥5% nuclear staining) in all cases of ACCs (100%) and negative (<5% nuclear staining) in all the cases of ACAs, leading to 100% sensitivity, specificity, PPV, and NPV of Ki67 positivity as a marker of malignancy. In ACAs, the mean Ki67% was 1.3% (range: 0.4–3.6), whereas in ACCs the mean Ki67% was significantly higher at 11.6%). There was a substantial extent of agreement between Ki 67 and SF-1 as a marker of malignancy. (kappa coefficient: 0.75)
P53 was positive in seven ACCs and negative two ACCs, whereas it was negative in all the ACAs, leading to 77.8% sensitivity, 100% specificity, 100% PPV, and 88.2% NPV of P53 positivity as a marker of malignancy. A comparative analysis of diagnostic indices of SF-1, Ki-67, and P53 immunoexpression is given in [Table 2] [Figure 4] and [Figure 5].
|Table 2: Comparative analysis of diagnostic indices of SF-1, Ki-67, and P53 immunoexpression|
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|Figure 4: a) ACA: Section shows the tumor with the intact capsule. (H&E, X40). 4b) ACA: Section shows a nest of cells with clear cytoplasm and a small nucleus. (H&E, X100). 4c) ACA: Section shows cells with clear cytoplasm; no pleomorphism or mitosis is identified. (H&E, X400). 4d) ACA: Section shows the absence of staining for p53. (IHC, X400). 4e) ACA: Section shows low Ki 67% LI (IHC, X400). 4f) ACA: A few cells show positivity for SF-1. (IHC, X400)|
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|Figure 5: a) ACC: Section shows capsular invasion by the tumor. (H&E, X40). Inset shows a low power view of the same. 5b) ACC: Section shows cells arranged in a diffuse pattern, exhibiting a high nuclear grade. (H&E, X100). 5c) ACC: Section shows cells with hyperchromatic and pleomorphic nuclei. (H&E, X400). 5d) ACC: Section shows p53 staining in more than 5% of cells. (IHC, X100). 5e) ACC: Section shows Ki 67 Li of more than 5%. (IHC, X400). 5f) ACC: The tumor cells show diffuse and strong positivity (3+) for SF-1. (IHC, X100). Inset shows a high power view of the same|
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| Discussion|| |
Adrenal masses are common tumors with ACA being the most common of these masses. ACC is a rare malignancy that can be diagnostically challenging. Many multiparametric scoring systems and diagnostic algorithms have been proposed to differentiate ACA from ACC. ACTs also need to be differentiated from other primary adrenal tumors like phaeochromocytoma as well as metastases to the adrenal gland. Myxoid, oncocytic, and sarcomatoid variants of ACCs must be recognized so that they are not misdiagnosed as other tumors. Various scoring systems that have come up include Weiss score, modified Weiss score, Van Slooten score, Helsinki score, Hough Reticulin algorithm of Volante, etc. Out of these, Weiss scoring system is the most widely used one. In addition to the interobserver variability in the application of the Weiss scoring system, this cannot be applied to certain variants of ACC such as oncocytic, sarcomatoid, and myxoid types and pediatric ACCs. Lin-Weiss-Bisceglia criteria have been proposed for oncocytic variant and pediatric ACCs, Wieneke criteria has been used., Myxoid and sarcomatoid ACCs are rare, and they do not have any separate scoring system. IHC is a useful modality with diagnostic and prognostic implications in ACCs. In this study, we investigated the expression of SF-1 in ACA and ACC. The aim of our study was to evaluate SF-1, as a diagnostic marker in differentiating between ACA and ACC as well as a prognostic marker in ACC. We also analyzed the extent of agreement between SF-1 and KI67 as a marker of ACC.
ACC has an annual incidence of 0.5 to 2.0 per million people. The male-to-female ratio of ACC is 1:1.2 to 1:1.5. The average age of presentation as reported in the United States National Cancer Data Base is 55 years. The average age of our series was 42 years with female preponderance and a male to female ratio of 1:2.
ACC has a variable clinical presentation. The majority of ACCs are biochemically functional, but in a large proportion of patients it does not manifest clinically, and in these patients, tumors are discovered incidentally or are metastatic at the time of presentation., The most common sites of metastasis are the liver, lungs, and bone. In the series by Wanis et al., six out of eight patients of ACC presented as incidentalomas, one patient had metastatic disease on presentation and one patient presented with Cushing's syndrome. In our study, out of fifteen ACAs nine were functional and six were nonfunctional. Out of nine ACCs, five were functional and four were nonfunctional. The most common presentation of ACTs was Cushing syndrome, and this was followed by incidentalomas.
Using Weiss criteria, we classified 15 cases as ACA and 9 cases as ACC. The difference in the number of cases with >33% of diffuse architecture and less than 25% of clear cytoplasm, between the ACC and ACA groups, was significant. In ACCs, the mean mitotic rate per 50 high power fields was significantly higher than ACA. There was a significant difference in expression of high nuclear grade, atypical mitotic figure, and necrosis between the ACC and ACA group. Capsular invasion, venous invasion, and sinusoidal invasion were significantly higher in ACC. In our study, out of all these features, the most significant findings in ACC were necrosis and capsular invasion.
The search for a consistent, reliable morphological diagnostic parameter for ACTs has led to diverse conclusions. In adult patients, the mitotic count has been shown to have the highest prognostic significance, with Weiss et al. have proposed a 2 tier grading system based on the mitotic count. Mitotic grading of ACTs has even been used by some authors as the gold standard in individualizing treatment plans for adult patients.,
Among several IHC markers proposed to confirm adrenocortical origin, SF-1 has attracted major interest. The adrenal gland and retroperitoneum can harbor various neoplasms that may cause diagnostic challenges. So, a biomarker has to be wisely chosen that has high sensitivity and specificity. SF-1 expression is a strong tool to identify the adrenocortical origin of a given tumoral lesion, irrespective of its nature. It is expressed only by a few other steroidogenic tissues such as the ovary, testes, and pituitary. Doghman et al. showed that SF-1 overexpression led to increased proliferation and decreased apoptosis of human adrenocortical cells. In a large study of adrenal neoplasms by Sbeira et al., the overall specificity of SF-1 was reported to be 100%. Sensitivity of SF-1 was reported as 100% in benign adrenal cortical proliferation (adrenal cortical hyperplasia and ACA), and 98% in ACC. In our study, we found SF-1 to be 100% sensitive and 80% specific in detecting ACCs with a PPV of 75% and NPV of 100%. There was a difference in expression of SF-1 between ACC and ACA which was significant. In ACAs, the mean SF-1 expression was 34.8%, whereas in ACCs the mean SF-1 expression was significantly higher at 87. Therefore, in addition to the identification of adrenocortical origin, SF-1 is useful in differentiating between ACA and ACC.
Sbeira et al., in their study noted that three out of their 161 functional ACCs did not show immunoreactivity for SF-1. They accounted for this as a methodical limitation of IHC. They hypothesized that this also might be a result of some activating mutations downstream of SF-1 pathway, and these cases could be truly SF-1 negative. In contrast to this, Duregon et al. detected SF-1 at a high expression level in around 40% of functioning but in only 9% of nonfunctioning ACCs. In their study, SF-1 was differentially expressed in ACC histologic types. It was slightly more expressed in myxoid ACC, compared with the conventional ones, and it was infrequently expressed in the oncocytic variant of ACC. They assumed that the differential expression of SF-1 was proportional to hormone production and secretion by tumor cells which made them conclude that SF-1 expression is a useful diagnostic tool, given that the results are corroborated with morphological and clinical findings as its sensitivity might be lower in some ACC variants and in nonfunctioning tumors. Wanis et al. described two sarcomatoid variants of ACCs that lacked SF-1 staining and suggested that there might be an alternate pathway of development of these tumors. Nevertheless, in our study, all nine of the ACCs showed grade 3 (positive) expression of SF-1 irrespective of being functional or nonfunctional. Out of the fifteen ACAs, three showed SF-1 positivity, but it is noteworthy that the grade was 2 in each of them. The remaining twelve ACAs showed grade 1 expression. The SF-1 expression did not correlate with the functional activity of ACTs.
SF-1 has potential implications in the prognostic characterization of ACC. Sbiera et al. provided the first evidence that high SF-1 expression is associated with poor clinical outcomes in adults with ACC. Duregon et al. showed that high expression levels of SF-1 in ACC were closely correlated with survival, mitotic, and proliferation indices. In our study, a Kaplan-Meier survival analysis showed similar findings where increased SF-1 expression correlated with worst survival. The negative association between SF-1 staining intensity and survival strengthens the concept that SF-1 is a crucial, dosage-dependent survival factor in ACC.
Figueiredo et al. used fluorescent in situ hybridization and comparative genomic hybridization to investigate the possible gain/amplification of the SF-1 gene in childhood ACTs which included six ACC and three ACA. They found a copy number gain of chromosomal region 9q34 in eight of the nine tumors. James et al. also reported a gain of 9q34 in ten out of eleven childhood tumors (nine ACA and two ACC), and Dohna et al. reported a gain involving the 9q34 region in eight ACA and 14 ACC.
Inverse agonists of SF-1 have been successfully studied in vitro on human ACC cells. Although it may have some clinical utility, this is yet to be trialed.
SF-1 is expressed in both benign and malignant ACTs, so it may seem contradictory that SF-1 has such a strong association with survival in ACC. However, it has been suggested that the action of SF-1 varies depending on the cellular context. In well-differentiated adrenocortical cells, SF-1 plays a part in steroidogenesis. SF-1 also plays a major role in fetal adrenal development by stimulating adrenal growth independent of its action on steroidogenesis. Sbeira et al. have hypothesized that in ACCs, the cellular environment resembles the fetal adrenal, whereas ACAs represent a differentiated phenotype. That the hormonal activity in their study did not correlate with SF-1 expression was in agreement with this hypothesis.
Ki 67 is a proliferation marker that is used as a prognostic indicator in many tumors. Ki-67 has steadily been reported useful in the differential diagnosis between ACC and ACA. Takehara et al. observed that Ki67LI was markedly higher in ACC than ACA in adults. Stojadinovic et al., reported a correlation between Ki67LI and Weiss scoring system. Duregon et al. showed that Ki67LI was the strongest predictor of overall survival in patients with ACC. In our study, in ACAs the mean Ki67LI was 1.3%, whereas in ACCs, the mean Ki67LI was significantly higher at 11.6%. Moreover, we established a moderate degree of agreement between Ki67LI and SF-1 as a marker of malignancy with the kappa coefficient being 0.75.
P53 plays a significant role in cell cycle progression and apoptosis pathway. P53 immunoreactivity has been found to well correlate with the presence of TP53 gene mutations, which is present in 25%–30% of sporadic ACCs, but not in ACAs. Thus, a good specificity, but a very low sensitivity makes p53 a diagnostic tool with limited value., In our study, P53 was 77.8% sensitive in detecting ACC, whereas it had 100% specificity and PPV. All the ACAs were negative for p53.
Several biomarkers other than SF-1 have been described for confirmation of adrenal cortical origin. Out of them, specificity and sensitivity rates of Melan A are very high, provided that a diagnosis of metastatic melanoma or primary adrenal PEComa has been excluded. Markers whose specificity and sensitivity are lower than those of SF-1 and Melan-A, include alpha-inhibin, calretinin, and D2–40. IGF-2 protein overexpression has been observed in a high number of ACCs and almost no ACAs, but the interpretation of IGF-2 is difficult.,,
Recently, transcriptomic and proteomic analysis, mRNA, and microRNA expression profiling studies have identified molecular markers of malignancy in ACTs. The imprinted gene IGF2 is overexpressed in childhood ACT, as compared with the normal adrenal gland, and it has a major role in regulating the growth of fetal and tumour adrenocortical cells. The IGF-mammalian target of the rapamycin (IGF-mTOR) signaling pathway has emerged as a major potential therapeutic target.
| Conclusion|| |
In this study, we have shown that in adult ACC, SF-1 has both diagnostic significance and prognostic implication. There is a negative association between SF-1 expression and survival which supports the concept that SF-1 is a crucial, dosage-dependent survival factor in ACC. A moderate degree of agreement exists between Ki67LI and SF-1 as a marker of ACC. A low sensitivity makes p53 a diagnostic tool with limited value in ACC.
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Conflicts of interest
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Department of Pathology, 244 AJC Bose Road, Institute of Post Graduate Medical Education and Research Kolkata, West Bengal - 700020
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2]