- Email: [email protected]
Does CD10 immunoexpression have a diagnostic utility in the differential diagnosis of renal oncocytomas and eosinophilic variants of chromophobe renal cell carcinomas?
CORRESPONDENCE
Young Kon Kim{ Young Bum Jeong{ Departments of *Pathology, {Radiology, and {Urology, Institute for Medical Science, Center for Healthcare Technology Development, Chonbuk National University Medical School, Korea Professor H. S. Park. E-mail: [email protected]
ACKNOWLEDGEMENT This work was supported by a grant of the Korean Ministry of Education, Science and Technology (The Regional Core Research Program/ Center for Healthcare Technology Development).
1. Forsthoefel KF. Myxoid adrenal cortical carcinoma. A case report with differential diagnostic considerations. Arch Pathol Lab Med 1994; 118: 1151–3. 2. Tang CK, Harriman BB, Toker C. Myxoid adrenal cortical carcinoma: a light and electron microscopic study. Arch Pathol Lab Med 1979; 103: 635–8. 3. Brown FM, Gaffey TA, Wold LE, Lloyd RV. Myxoid neoplasms of the adrenal cortex: a rare histologic variant. Am J Surg Pathol 2000; 24: 396–401. 4. Honda K, Kashima K, Daa T, Gamachi A, Nakayama I, Yokoyama S. Myxoid adrenal cortical adenoma. Pathol Int 2001; 51: 887–91. 5. Dundr P, Nova´k K. Pseudoglandular myxoid adenoma of the adrenal gland. Pathol Res Pract 2003; 199: 493–6. 6. Bollito ER, Papotti M, Porpiglia F, et al. Myxoid adrenocortical adenoma with a pseudoglandular pattern. Virchows Arch 2004; 445: 414–8. 7. Carney JA, Gordon H, Carpenter PC, Shenoy BV, Go VL. The complex of myxomas, spotty pigmentation, and endocrine overactivity. Medicine (Baltimore) 1985; 64: 270–83. 8. Forsthoefel KF. Myxoid adrenal cortical carcinoma. A case report with differential diagnostic considerations. Arch Pathol Lab Med 1994; 118: 1151–3. 9. Barnett CC, Varma DG, El-Naggar AK, et al. Limitations of size as a criterion in the evaluation of adrenal cortical tumors. Surgery 2000; 128: 973–82. 10. Weiss LM. Comparative histologic study of 43 metastasizing and nonmetastasizing adrenocortical tumors. Am J Surg Pathol 1984; 8: 163–9. 11. Weiss LM, Medeiros LJ, Vickery AL Jr. Pathologic features of prognostic significance in adrenocortical carcinoma. Am J Surg Pathol 1989; 13: 202–6.
DOI: 10.1080/00313020802579300
Does CD10 immunoexpression have a diagnostic utility in the differential diagnosis of renal oncocytomas and eosinophilic variants of chromophobe renal cell carcinomas? Sir, Nowadays, more renal tumours are detected incidentally due to the improvement in radiological modalities. As a result, surgeons require the distinction of eosinophilic variant of chromophobe renal cell carcinomas (RCCs) and renal oncocytomas (ROs) in Tru-cut biopsies for performing nephron sparing surgery. What is more, this distinction sometimes poses a diagnostic difficulty in H&E
191
sections. However, diffuse staining with Hale’s colloidal iron (HCI) stain and ultrastructural demonstration of chromophobe type microvesicles are still accepted as the most important criteria for the diagnosis of chromophobe RCCs.1 Although HCI staining plays an important role in the absence of some technical problems, it lacks sensitivity.1 On the other hand, ultrastructural studies cannot be performed easily. For this reason, many immunomarkers have been studied for the differential diagnosis between chromophobe RCCs and ROs in recent years. CD10, which is a cell surface metalloproteinase localised to the proximal nephron of the kidney, has been considered a useful marker in the differential diagnosis of RCC, because of its high level of expression in clear cell and papillary RCCs and its absence in chromophobe RCC.2–9 On the other hand, a number of studies have shown that CD10 is expressed in ROs and chromophobe RCCs.2,7,9,10 Recently, we have stated that apical and/or polar CD63 (a lysosomal membrane glycoprotein) immunostaining had 95% sensitivity and 100% specificity to diagnose ROs.1 However, the conflicting CD10 immunostaining results of previous studies led us to perform this study. We aimed to investigate the usefulness of CD10 and to compare it with CD63 in the differential diagnosis of ROs and eosinophilic variants of chromophobe RCCs. A total of 85 resected eosinophilic renal epithelial tumours (53 ROs and 32 eosinophilic variants of chromophobe RCCs) were included in this study. Routine immunohistochemical staining was performed on formalinfixed, paraffin-embedded tissues using the streptavidin– biotin complex method. The primary antibodies which were applied are as follows: anti-CD63 (monoclonal, mouse antihuman, clone NKI/C3, 1:100, 60 min; NeoMarkers, USA) and anti-CD10 antibodies (monoclonal, mouse antihuman, clone 56C6, 1:10, 120 min; Novocastra Laboratories, UK). The results of immunohistochemical staining were recorded as positive (410% of tumour cells staining) or negative, and when appropriate, the staining pattern (cytoplasmic diffuse, cytoplasmic apical and/or polar, cytoplasmic disperse-irregular and membranous) was noted. The results of the staining pattern are summarised in Table 1 (Fig. 1 and 2). TABLE 1 Cytoplasmic distribution of the immunoreactivities Renal oncocytomas n (%)
Chromophobe RCCs n (%)
Total CD63* No staining Diffuse Apical and/or polar Disperse-irregular Membranous
53 53 0 1 51 1 0
(100) (100) (0) (2) (96) (2) (0)
32 32 0 31 0 1 0
(100) (100) (0) (97) (0) (3) (0)
CD10* No staining Diffuse Focal cytoplasmic Disperse-irregular Membranous
12 41 7 4 1 0
(23) (77) (13) (8) (2) (0)
8 24 2 4 2 0
(25) (75) (6) (13) (6) (0)
*Number of cases which were positive out of total. RCCs, renal cell carcinomas.
192
Pathology (2009), 41(2), Month
CORRESPONDENCE
FIG. 1 (a) Focal positive immunostaining in renal oncocytomas. (b) Diffuse positive immunostaining in eosinophilic variant chromophobe RCCs. (c) Positive immunostaining in the proximal tubular epithelium and glomerular cells in non-neoplastic renal parenchyma (anti-CD10).
FIG. 2 (a) Diffuse positive immunostaining in eosinophilic variant chromophobe RCCs. (b) Apical/polar cytoplasmic immunostaining in renal oncocytomas (anti-CD63).
Previous results regarding CD10 are conflicting in this field2–10 (Table 2). According to these, its expression varied from 0% to 67% in ROs and from 0% to 100% in chromophobe RCCs (Table 2). Some authors give a diagnostic importance to the negativity of CD10 in ROs,2–9 but in our study, we detected the expression of CD10 in 25% of chromophobe RCCs and 23% of ROs. Our results showed that CD10 is not a specific marker for diagnosing clear cell RCC, as its expression was also present in ROs and chromophobe RCCs. Although CD10 is known to be localised to the proximal nephron of the kidney, its expression was also observed in the collecting duct cells of the kidney between the 16th and 23rd weeks of intrauterine life.6 This finding could also explain the presence of CD10 immunostaining in ROs and chromophobe RCCs, which are believed to have originated from intercalated cells of the collecting duct. Another point worth stressing is that we have not found any membranous staining pattern, which is classically described in clear cell RCCs. However, this characteristic membranous staining may have a potential utility in the differentiation of eosinophilic clear cell RCCs from eosinophilic variant of chromophobe RCCs and ROs. On the other hand, Wang et al.9 and Abrahams et al.2 also reported the presence of membranous immunoreactivity in chromophobe RCCs and ROs.
TABLE 2 CD10 immunostaining results by study2–10 Positive/total cases (%) Study Kim and Kim4 Wang and Mills9 Pan et al.8 Langner et al.5 Abrahams et al.2 Martignoni et al.6 Avery et al.3 Mazal et al.7 Liu et al.10 Mete et al. (present study)
Chromophobe RCCs 0/6 8/11 9/28 11/28 24/24 11/42 0/19 1/24 10/22 8/32
(0) (73) (32) (48) (100) (26) (0) (4) (45) (25)
Renal oncocytomas 3/12 (25) 7/12 (58) 0/7 (0) Not studied 4/6 (67) Not studied 3/9 (33) 1/29 (3.5) 5/17 (29) 12/53 (23)
RCCs, renal cell carcinomas.
One important technical issue that should be noted, when interpreting the immunohistochemical results in eosinophilics tumours such as ROs, is that they are prone to show non-specific adsorption during conventional immunohistochemical procedures.1 Therefore, positive results must be assessed with caution. The latter may explain the presence of focal and faint non-specific immunostaining in some studies. Apart from CD10, many other markers such as cytokeratins, epithelial membrane antigen, parvalbumin,
CORRESPONDENCE
caveolins, anti-mitochondrial antibody, CD117, RCC, AMACR, Pax-2, cadherins, EpCAM, BerEP4, and MOC31 have been studied in the differential diagnosis of ROs and chromophobe RCCs.2–10 However, we have previously found that apical and/or polar CD63 staining was found to be statistically significant for ROs when comparing with chromophobe RCCs, which were characterised by a diffuse cytoplasmic CD63 staining. The present study showed that the sensitivity and specificity of apical and/or polar CD63 immunostaining were 96% and 100%, respectively. Briefly, based on our study, CD10 cannot be used for differentiating ROs from chromophobe RCCs, and its expression does not rule out the possibility of ROs. As a conclusion, we strongly advise using anti-CD63 immunostaining when standard diagnostic criteria are not helpful to differentiate ROs from eosinophilic variants of chromophobe RCCs. Ozgur Mete Isın Kilicaslan Veli Uysal Istanbul University, Istanbul Faculty Department of Pathology, Turkey
of
Medicine,
Dr O. Mete. E-mail: [email protected] ACKNOWLEDGEMENT This work was supported by the Research Fund of Istanbul University. Project number: UDP-836/27062006. The results of this study were partially presented in the poster session of the XXVI Congress of the International Academy of Pathology (Montreal, 16–21 September, 2006)
1. Mete O, Kilicaslan I, Gulluoglu MG, Uysal V. Can renal oncocytoma be differentiated from its renal mimics? The utility of antimitochondrial, caveolin-1, CD63 and cytokeratin 14 antibodies in the differential diagnosis. Virchows Arch 2005; 447; 938–46. 2. Abrahams NA, MacLennan GT, Khoury JD, et al. Chromophobe renal cell carcinoma: a comparative study of histological, immunohistochemical and ultrastructural features using high throughput tissue micoarray. Histopathology 2004; 45; 593–602. 3. Avery AK, Beckstead J, Renshaw AA, Corless CL. Use of antibodies to RCC and CD10 in the differential diagnosis of renal neoplasms. Am J Surg Pathol 2000; 24; 203–10. 4. Kim MK, Kim S. Immunohistochemical profile of common epithelial neoplasms arising in the kidney. Appl Immunohistochem Mol Morphol 2002; 10; 332–8. 5. Langner C, Ratschek M, Rehak P, et al. CD10 is a diagnostic and prognostic marker in renal malignancies. Histopathology 2004; 45; 460–7. 6. Martignoni G, Pea M, Brunelli M, et al. CD10 expression in a subset of chromophobe renal cell carcinomas. Mod Pathol 2004; 17; 1455–63. 7. Mazal PR, Stichenwirth M, Koller A, et al. Expression of aquaporins and PAX-2 compared to CD10 and cytokeratin 7 in renal neoplasms: a tissue microarray study. Mod Pathol 2005; 18; 535–40. 8. Pan CC, Chen PCH, Ho DMT. The diagnostic utility of MOC31, BerEP4, RCC marker and CD10 in the classification of renal cell carcinoma and renal oncocytoma: an immunohistochemical analysis of 328 cases. Histopathology 2004; 45; 452–9. 9. Wang HY, Mills S. KIT and RCC are useful in distinguishing chromophobe RCC from the granular variant of clear cell RCC. Am J Surg Pathol 2005; 29; 640–6. 10. Liu L, Qian J, Singh H, et al. Immunohistochemical analysis of chromophobe renal cell carcinoma, renal oncocytoma, and clear cell carcinoma: An optimal and practical panel for differential diagnosis. Arch Pathol Lab Med 2007; 131; 1290–7.
DOI: 10.1080/00313020802579334
193
Expression of c-kit in hydatidiform mole Sir, Hydatidiform mole (HM) comprises two distinct subtypes—complete and partial moles—and represents a unique group of diseases in which the lesions are derived from the conceptus and not from the patient/mother.1,2 Both paternal and maternal genomic contributions to the conceptual genome are necessary for the normal development of both embryonic and extra-embryonic tissues,3 but disruption of the balance of genomic imprinting may lead to hyperplastic proliferation of the trophoblast which characterises molar pregnancies.4 HM can be considered as a premalignant lesion with both subtypes lacking fetal development but having malignant potential. The pathogenesis of molar pregnancies is largely unknown but thought to be similar to neoplastic processes in other parts of the body in that it is a multistep process involving the accumulation of several genetic events including activation of oncogenes and/or loss of tumour suppressor genes.2 To better define the underlying pathogenesis of complete and partial moles, we studied the expression of c-kit in complete and partial moles compared with normal termination of pregnancies. c-kit (KIT, CD117) is a tyrosine kinase receptor which regulates cell proliferation, apoptosis, adhesion, and chemotaxis: over-expression of ckit has also been implicated in tumour formation in other parts of the body.5 c-kit is thought to be involved in the normal differentiation of the placenta and is expressed in invading trophoblast, while its ligand, SCF (stem cell factor), is detected in placental fibroblasts, invasive extravillous trophoblast and maternal decidual spiral arteries.6 Seven cases of complete HM (CHM) and seven partial HM (PHM) that had recorded b-hCG levels and/or cytogenetic reports and seven terminations of pregnancy (TOP) were selected for the study. Immunohistochemistry was performed using the streptavidin biotin complex immunoperoxidase method (Chemicon, Australia). Antigen retrieval was performed by microwave heating in 1 mM pH 8 EDTA buffer for 10 min for c-kit (1:50 dilution; Cell Marque, USA) and in 1 mM pH 6 citrate buffer for 12 min for p57 (1:100 dilution; Novocastra, UK), the latter to confirm mole status.7 Sections of mast cell tumour were used as positive control for c-kit. Five fields were viewed at random for each specimen. Staining was assessed semi-quantitatively. Staining intensity was recorded on a seven-point scale: (0, 0–1, 1, 1þ, 2, 2þ, 3), 0, no staining; 1, very light staining weaker than the positive control; 2, moderate staining, as strong as the positive control sample; 3, very intense staining exceeding the positive control sample. The cells were distinguished as syncytiotrophoblast, cytotrophoblast, and extravillous trophoblast, and were given a grade of A (0–25%), B (25–75%), or C (75–99%) to quantify the number of cells stained. The average staining score for each specimen was calculated as the average of the five fields which was then rounded to the nearest interval of 0.5 to allow results to be interpreted using the seven-point scale. A univariate analysis of variance and a post-hoc analysis, using Tukey’s multiple comparison tests, were used to detect
Young Kon Kim{ Young Bum Jeong{ Departments of *Pathology, {Radiology, and {Urology, Institute for Medical Science, Center for Healthcare Technology Development, Chonbuk National University Medical School, Korea Professor H. S. Park. E-mail: [email protected]
ACKNOWLEDGEMENT This work was supported by a grant of the Korean Ministry of Education, Science and Technology (The Regional Core Research Program/ Center for Healthcare Technology Development).
1. Forsthoefel KF. Myxoid adrenal cortical carcinoma. A case report with differential diagnostic considerations. Arch Pathol Lab Med 1994; 118: 1151–3. 2. Tang CK, Harriman BB, Toker C. Myxoid adrenal cortical carcinoma: a light and electron microscopic study. Arch Pathol Lab Med 1979; 103: 635–8. 3. Brown FM, Gaffey TA, Wold LE, Lloyd RV. Myxoid neoplasms of the adrenal cortex: a rare histologic variant. Am J Surg Pathol 2000; 24: 396–401. 4. Honda K, Kashima K, Daa T, Gamachi A, Nakayama I, Yokoyama S. Myxoid adrenal cortical adenoma. Pathol Int 2001; 51: 887–91. 5. Dundr P, Nova´k K. Pseudoglandular myxoid adenoma of the adrenal gland. Pathol Res Pract 2003; 199: 493–6. 6. Bollito ER, Papotti M, Porpiglia F, et al. Myxoid adrenocortical adenoma with a pseudoglandular pattern. Virchows Arch 2004; 445: 414–8. 7. Carney JA, Gordon H, Carpenter PC, Shenoy BV, Go VL. The complex of myxomas, spotty pigmentation, and endocrine overactivity. Medicine (Baltimore) 1985; 64: 270–83. 8. Forsthoefel KF. Myxoid adrenal cortical carcinoma. A case report with differential diagnostic considerations. Arch Pathol Lab Med 1994; 118: 1151–3. 9. Barnett CC, Varma DG, El-Naggar AK, et al. Limitations of size as a criterion in the evaluation of adrenal cortical tumors. Surgery 2000; 128: 973–82. 10. Weiss LM. Comparative histologic study of 43 metastasizing and nonmetastasizing adrenocortical tumors. Am J Surg Pathol 1984; 8: 163–9. 11. Weiss LM, Medeiros LJ, Vickery AL Jr. Pathologic features of prognostic significance in adrenocortical carcinoma. Am J Surg Pathol 1989; 13: 202–6.
DOI: 10.1080/00313020802579300
Does CD10 immunoexpression have a diagnostic utility in the differential diagnosis of renal oncocytomas and eosinophilic variants of chromophobe renal cell carcinomas? Sir, Nowadays, more renal tumours are detected incidentally due to the improvement in radiological modalities. As a result, surgeons require the distinction of eosinophilic variant of chromophobe renal cell carcinomas (RCCs) and renal oncocytomas (ROs) in Tru-cut biopsies for performing nephron sparing surgery. What is more, this distinction sometimes poses a diagnostic difficulty in H&E
191
sections. However, diffuse staining with Hale’s colloidal iron (HCI) stain and ultrastructural demonstration of chromophobe type microvesicles are still accepted as the most important criteria for the diagnosis of chromophobe RCCs.1 Although HCI staining plays an important role in the absence of some technical problems, it lacks sensitivity.1 On the other hand, ultrastructural studies cannot be performed easily. For this reason, many immunomarkers have been studied for the differential diagnosis between chromophobe RCCs and ROs in recent years. CD10, which is a cell surface metalloproteinase localised to the proximal nephron of the kidney, has been considered a useful marker in the differential diagnosis of RCC, because of its high level of expression in clear cell and papillary RCCs and its absence in chromophobe RCC.2–9 On the other hand, a number of studies have shown that CD10 is expressed in ROs and chromophobe RCCs.2,7,9,10 Recently, we have stated that apical and/or polar CD63 (a lysosomal membrane glycoprotein) immunostaining had 95% sensitivity and 100% specificity to diagnose ROs.1 However, the conflicting CD10 immunostaining results of previous studies led us to perform this study. We aimed to investigate the usefulness of CD10 and to compare it with CD63 in the differential diagnosis of ROs and eosinophilic variants of chromophobe RCCs. A total of 85 resected eosinophilic renal epithelial tumours (53 ROs and 32 eosinophilic variants of chromophobe RCCs) were included in this study. Routine immunohistochemical staining was performed on formalinfixed, paraffin-embedded tissues using the streptavidin– biotin complex method. The primary antibodies which were applied are as follows: anti-CD63 (monoclonal, mouse antihuman, clone NKI/C3, 1:100, 60 min; NeoMarkers, USA) and anti-CD10 antibodies (monoclonal, mouse antihuman, clone 56C6, 1:10, 120 min; Novocastra Laboratories, UK). The results of immunohistochemical staining were recorded as positive (410% of tumour cells staining) or negative, and when appropriate, the staining pattern (cytoplasmic diffuse, cytoplasmic apical and/or polar, cytoplasmic disperse-irregular and membranous) was noted. The results of the staining pattern are summarised in Table 1 (Fig. 1 and 2). TABLE 1 Cytoplasmic distribution of the immunoreactivities Renal oncocytomas n (%)
Chromophobe RCCs n (%)
Total CD63* No staining Diffuse Apical and/or polar Disperse-irregular Membranous
53 53 0 1 51 1 0
(100) (100) (0) (2) (96) (2) (0)
32 32 0 31 0 1 0
(100) (100) (0) (97) (0) (3) (0)
CD10* No staining Diffuse Focal cytoplasmic Disperse-irregular Membranous
12 41 7 4 1 0
(23) (77) (13) (8) (2) (0)
8 24 2 4 2 0
(25) (75) (6) (13) (6) (0)
*Number of cases which were positive out of total. RCCs, renal cell carcinomas.
192
Pathology (2009), 41(2), Month
CORRESPONDENCE
FIG. 1 (a) Focal positive immunostaining in renal oncocytomas. (b) Diffuse positive immunostaining in eosinophilic variant chromophobe RCCs. (c) Positive immunostaining in the proximal tubular epithelium and glomerular cells in non-neoplastic renal parenchyma (anti-CD10).
FIG. 2 (a) Diffuse positive immunostaining in eosinophilic variant chromophobe RCCs. (b) Apical/polar cytoplasmic immunostaining in renal oncocytomas (anti-CD63).
Previous results regarding CD10 are conflicting in this field2–10 (Table 2). According to these, its expression varied from 0% to 67% in ROs and from 0% to 100% in chromophobe RCCs (Table 2). Some authors give a diagnostic importance to the negativity of CD10 in ROs,2–9 but in our study, we detected the expression of CD10 in 25% of chromophobe RCCs and 23% of ROs. Our results showed that CD10 is not a specific marker for diagnosing clear cell RCC, as its expression was also present in ROs and chromophobe RCCs. Although CD10 is known to be localised to the proximal nephron of the kidney, its expression was also observed in the collecting duct cells of the kidney between the 16th and 23rd weeks of intrauterine life.6 This finding could also explain the presence of CD10 immunostaining in ROs and chromophobe RCCs, which are believed to have originated from intercalated cells of the collecting duct. Another point worth stressing is that we have not found any membranous staining pattern, which is classically described in clear cell RCCs. However, this characteristic membranous staining may have a potential utility in the differentiation of eosinophilic clear cell RCCs from eosinophilic variant of chromophobe RCCs and ROs. On the other hand, Wang et al.9 and Abrahams et al.2 also reported the presence of membranous immunoreactivity in chromophobe RCCs and ROs.
TABLE 2 CD10 immunostaining results by study2–10 Positive/total cases (%) Study Kim and Kim4 Wang and Mills9 Pan et al.8 Langner et al.5 Abrahams et al.2 Martignoni et al.6 Avery et al.3 Mazal et al.7 Liu et al.10 Mete et al. (present study)
Chromophobe RCCs 0/6 8/11 9/28 11/28 24/24 11/42 0/19 1/24 10/22 8/32
(0) (73) (32) (48) (100) (26) (0) (4) (45) (25)
Renal oncocytomas 3/12 (25) 7/12 (58) 0/7 (0) Not studied 4/6 (67) Not studied 3/9 (33) 1/29 (3.5) 5/17 (29) 12/53 (23)
RCCs, renal cell carcinomas.
One important technical issue that should be noted, when interpreting the immunohistochemical results in eosinophilics tumours such as ROs, is that they are prone to show non-specific adsorption during conventional immunohistochemical procedures.1 Therefore, positive results must be assessed with caution. The latter may explain the presence of focal and faint non-specific immunostaining in some studies. Apart from CD10, many other markers such as cytokeratins, epithelial membrane antigen, parvalbumin,
CORRESPONDENCE
caveolins, anti-mitochondrial antibody, CD117, RCC, AMACR, Pax-2, cadherins, EpCAM, BerEP4, and MOC31 have been studied in the differential diagnosis of ROs and chromophobe RCCs.2–10 However, we have previously found that apical and/or polar CD63 staining was found to be statistically significant for ROs when comparing with chromophobe RCCs, which were characterised by a diffuse cytoplasmic CD63 staining. The present study showed that the sensitivity and specificity of apical and/or polar CD63 immunostaining were 96% and 100%, respectively. Briefly, based on our study, CD10 cannot be used for differentiating ROs from chromophobe RCCs, and its expression does not rule out the possibility of ROs. As a conclusion, we strongly advise using anti-CD63 immunostaining when standard diagnostic criteria are not helpful to differentiate ROs from eosinophilic variants of chromophobe RCCs. Ozgur Mete Isın Kilicaslan Veli Uysal Istanbul University, Istanbul Faculty Department of Pathology, Turkey
of
Medicine,
Dr O. Mete. E-mail: [email protected] ACKNOWLEDGEMENT This work was supported by the Research Fund of Istanbul University. Project number: UDP-836/27062006. The results of this study were partially presented in the poster session of the XXVI Congress of the International Academy of Pathology (Montreal, 16–21 September, 2006)
1. Mete O, Kilicaslan I, Gulluoglu MG, Uysal V. Can renal oncocytoma be differentiated from its renal mimics? The utility of antimitochondrial, caveolin-1, CD63 and cytokeratin 14 antibodies in the differential diagnosis. Virchows Arch 2005; 447; 938–46. 2. Abrahams NA, MacLennan GT, Khoury JD, et al. Chromophobe renal cell carcinoma: a comparative study of histological, immunohistochemical and ultrastructural features using high throughput tissue micoarray. Histopathology 2004; 45; 593–602. 3. Avery AK, Beckstead J, Renshaw AA, Corless CL. Use of antibodies to RCC and CD10 in the differential diagnosis of renal neoplasms. Am J Surg Pathol 2000; 24; 203–10. 4. Kim MK, Kim S. Immunohistochemical profile of common epithelial neoplasms arising in the kidney. Appl Immunohistochem Mol Morphol 2002; 10; 332–8. 5. Langner C, Ratschek M, Rehak P, et al. CD10 is a diagnostic and prognostic marker in renal malignancies. Histopathology 2004; 45; 460–7. 6. Martignoni G, Pea M, Brunelli M, et al. CD10 expression in a subset of chromophobe renal cell carcinomas. Mod Pathol 2004; 17; 1455–63. 7. Mazal PR, Stichenwirth M, Koller A, et al. Expression of aquaporins and PAX-2 compared to CD10 and cytokeratin 7 in renal neoplasms: a tissue microarray study. Mod Pathol 2005; 18; 535–40. 8. Pan CC, Chen PCH, Ho DMT. The diagnostic utility of MOC31, BerEP4, RCC marker and CD10 in the classification of renal cell carcinoma and renal oncocytoma: an immunohistochemical analysis of 328 cases. Histopathology 2004; 45; 452–9. 9. Wang HY, Mills S. KIT and RCC are useful in distinguishing chromophobe RCC from the granular variant of clear cell RCC. Am J Surg Pathol 2005; 29; 640–6. 10. Liu L, Qian J, Singh H, et al. Immunohistochemical analysis of chromophobe renal cell carcinoma, renal oncocytoma, and clear cell carcinoma: An optimal and practical panel for differential diagnosis. Arch Pathol Lab Med 2007; 131; 1290–7.
DOI: 10.1080/00313020802579334
193
Expression of c-kit in hydatidiform mole Sir, Hydatidiform mole (HM) comprises two distinct subtypes—complete and partial moles—and represents a unique group of diseases in which the lesions are derived from the conceptus and not from the patient/mother.1,2 Both paternal and maternal genomic contributions to the conceptual genome are necessary for the normal development of both embryonic and extra-embryonic tissues,3 but disruption of the balance of genomic imprinting may lead to hyperplastic proliferation of the trophoblast which characterises molar pregnancies.4 HM can be considered as a premalignant lesion with both subtypes lacking fetal development but having malignant potential. The pathogenesis of molar pregnancies is largely unknown but thought to be similar to neoplastic processes in other parts of the body in that it is a multistep process involving the accumulation of several genetic events including activation of oncogenes and/or loss of tumour suppressor genes.2 To better define the underlying pathogenesis of complete and partial moles, we studied the expression of c-kit in complete and partial moles compared with normal termination of pregnancies. c-kit (KIT, CD117) is a tyrosine kinase receptor which regulates cell proliferation, apoptosis, adhesion, and chemotaxis: over-expression of ckit has also been implicated in tumour formation in other parts of the body.5 c-kit is thought to be involved in the normal differentiation of the placenta and is expressed in invading trophoblast, while its ligand, SCF (stem cell factor), is detected in placental fibroblasts, invasive extravillous trophoblast and maternal decidual spiral arteries.6 Seven cases of complete HM (CHM) and seven partial HM (PHM) that had recorded b-hCG levels and/or cytogenetic reports and seven terminations of pregnancy (TOP) were selected for the study. Immunohistochemistry was performed using the streptavidin biotin complex immunoperoxidase method (Chemicon, Australia). Antigen retrieval was performed by microwave heating in 1 mM pH 8 EDTA buffer for 10 min for c-kit (1:50 dilution; Cell Marque, USA) and in 1 mM pH 6 citrate buffer for 12 min for p57 (1:100 dilution; Novocastra, UK), the latter to confirm mole status.7 Sections of mast cell tumour were used as positive control for c-kit. Five fields were viewed at random for each specimen. Staining was assessed semi-quantitatively. Staining intensity was recorded on a seven-point scale: (0, 0–1, 1, 1þ, 2, 2þ, 3), 0, no staining; 1, very light staining weaker than the positive control; 2, moderate staining, as strong as the positive control sample; 3, very intense staining exceeding the positive control sample. The cells were distinguished as syncytiotrophoblast, cytotrophoblast, and extravillous trophoblast, and were given a grade of A (0–25%), B (25–75%), or C (75–99%) to quantify the number of cells stained. The average staining score for each specimen was calculated as the average of the five fields which was then rounded to the nearest interval of 0.5 to allow results to be interpreted using the seven-point scale. A univariate analysis of variance and a post-hoc analysis, using Tukey’s multiple comparison tests, were used to detect