Immunohistochemical localization of gross cystic disease fluid protein-15, -24 and -44 in ductal carcinoma in situ of the breast: relationship to the degree of differentiation

AIMS: Three major proteins present in breast gross cystic disease fluid and expressed by the cyst lining apocrine epithelium are gross cystic disease fluid protein-15 (GCDFP-15), apolipoprotein-D (APO-D; GCDFP-24) and zinc alpha2-glycoprotein (ZnGP; GCDFP-44). The aim of this study was to investigate the expression of these proteins in ductal carcinoma in situ (DCIS) of the breast and to relate their expression with the degree of differentiation of DCIS. METHODS AND RESULTS: An immunohistochemical study of these proteins was performed in 57 cases of DCIS and nine cases of morphologically apocrine DCIS. Positivity was seen in 24/57 (42.1%) cases with anti-GCDFP-15, 20/57 (35.1%) cases with anti-GCDFP-24 and 22/57 (38.6%) cases with anti-GCDFP-44. GCDFP-15 positivity was noted in 5/13 (38.5%) of the well-differentiated, 11/19 (57.9%) intermediately differentiated and 8/25 (32.0%) of the poorly differentiated cases (P=0.217). GCDFP-24 positivity was seen in 3/13 (23.0%) well-differentiated, 9/19 (47.4%) intermediately differentiated and 8/25 (32.0%) poorly differentiated cases (P=0.336). GCDFP-44 was detected in 5/13 (38.5%) of well-differentiated cases, 11/19 (57.9%) intermediately differentiated and 6/25 (24.0%) poorly differentiated cases (P=0.074). In the nine cases of apocrine DCIS, GCDFP-15 positivity was detected in seven (77.8%), while five (55.6%) and six (66.7%) cases were positive for GCDFP-24 and GCDFP-44, respectively. CONCLUSIONS: The results indicate that there is no significant association between the expression of the studied proteins and the degree of differentiation of DCIS of the breast. Moreover, some morphologically apocrine DCIS cases appear to lose expression of these proteins.     

Diagnostic utility of mammaglobin and GCDFP‐15 in the identification of metastatic breast carcinoma in fluid specimens

Morphologic differentiation of breast carcinoma from nonmammary malignancies in fluid specimens can be a diagnostic challenge. Immunocytochemistry is often employed in the differential diagnosis. In this study, we evaluated the expression of mammoglobin (MGB1) in body‐cavity fluid specimens and compared its efficacy as a marker for metastatic breast carcinomas with that of gross cystic disease fluid protein‐15 (GCDFP‐15). Cell blocks from 40 fluid specimens were immunostained with monoclonal antibodies against MGB1 and GCDFP‐15. They included 15 breast carcinomas and 25 nonmammary carcinomas (10 lungs, 10 ovaries, 3 gastrointestinal tracts, 1 kidney, and 1 urinary bladder). Positivity was defined as the presence of cytoplasmic staining in 10% or more carcinoma cells. Thirteen (87%) and seven (47%) breast carcinomas showed positive staining with MGB1 and GCDFP‐15, respectively. Three (12%) nonmammary carcinomas (2 ovarian and 1 colonic) showed positive MGB1 staining; one (3%) nonmammary carcinoma demonstrated positive GCDFP‐15 staining. The differences of MGB1 and GCDFP‐15 staining between breast and nonmammary carcinomas were statistically significant (P < 0.05). Both MGB1 and GCDFP‐15 are specific markers for metastatic breast carcinomas in cell block fluid specimens (88 vs. 96%). However, MGB1 is more sensitive than GCDFP‐15 as a marker for metastatic breast carcinoma (87 vs. 46%). Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Evaluation of androgen receptor and GATA binding protein 3 as immunohistochemical markers in the diagnosis of metastatic breast carcinoma to the lung

Differentiating metastatic breast carcinoma in the lungs from primary lung tumors and mesotheliomas is important for determining prognosis and treatment. We evaluated novel breast specific markers, androgen receptor (AR) and GATA binding protein 3 (GATA3) immunohistostaining, for this differential, and compare to other traditional markers. The specimens comprised 33 metastatic breast carcinomas to the lung, 566 primary lung tumors (170 adenocarcinomas, 157 squamous cell carcinomas, 31 pleomorphic carcinomas, 115 large cell neuroendocrine carcinomas, 43 small cell carcinomas, and 49 typical carcinoids) and 42 malignant mesotheliomas. They were analyzed by immunohistochemistry using antibodies to AR, GATA3, estrogen receptor (ER), progesterone receptor (PgR), mammaglobin, gross cystic disease fluid protein‐15 (GCDFP‐15). Of the metastatic breast carcinomas, immunohistostaining of AR, GATA3, ER, PgR, mammaglobin, GCDFP‐15 were positive in 27 cases (81.8%), 24 cases (72.7%), 26 cases (78.8%), 13 cases (39.4%), 12 cases (36.4%), 9 cases (27.3%), respectively. Of primary lung tumors and mesotheliomas, staining of AR, GATA3, ER, PgR, mammaglobin, GCDFP‐15 were positive in 18 cases (3%), 3 cases (0.5%), 4 cases (0.7%), 2 cases (0.3%), 0 case (0%), 2 cases (0.3%), respectively. Immunohistochemistry of AR and GATA3 are reliable for differentiating metastatic breast carcinoma from primary lung tumors and mesotheliomas.     

Encapsulated apocrine papillary carcinoma of the breast: Case report with clinicopathologic and immunohistochemical study

We describe a case of encapsulated papillary carcinoma (EPC), apocrine variant in a 50‐year‐old woman. The patient presented a cystic lesion in her right breast, measuring 8 cm in diameter, containing three solid papillary nodules. A fine‐needle aspiration showed isolated apocrine cells containing round nuclei, irregular nuclear membranes, fine chromatin, and prominent macronucleoli. The lesion was excised and showed a pure papillary apocrine carcinoma, which stained diffusely with GCDFP‐15 and androgen receptors. The lesion was totally devoid of myoepithelial cells (smooth muscle actyn, p63, calponin, and collagen IV stains were negative). With MIB1 the proliferative activity was 10%. To the best of our knowledge, this is the first report of EPC apocrine variant with cytologic and immunohistochemical study. This lesion must be included in the list of apocrine lesions of the breast. Diagn. Cytopathol. 2010. © 2010 Wiley‐Liss, Inc.     

Gross cystic disease fluid protein‐15 and mammaglobin A expression determined by immunohistochemistry is of limited utility in triple‐negative breast cancer

Aims: In addition to oestrogen and progesterone receptors, gross cystic disease fluid protein‐15 (GCDFP‐15) and mammaglobin A (MAM) are the most common markers used to identify breast origin by immunohistochemistry. GCDFP‐15 expression has been reported in approximately 60% of breast carcinomas and MAM expression in approximately 80%. Data on their expression in triple‐negative breast cancer (TNBC) are very limited. The aim of this study was to examine the expression of these markers in TNBC to determine their utility in pathological diagnosis. Methods and results: We studied the immunohistochemical (IHC) expression of GCDFP‐15 and MAM in 63 primary and 118 metastatic TNBCs. GCDFP‐15 staining was present in 14% of primary and 21% of metastatic TNBCs. MAM staining was present in 25% of primary and 41% of metastatic TNBCs. The frequency of expression of GCDFP‐15 and/or MAM was 30% in primary and 43% in metastatic TNBCs, and many positive tumours had only focal staining. Conclusions: Staining for GCDFP‐15 and/or MAM in triple‐negative carcinomas helps to confirm breast origin, but most tumours in this subgroup of breast carcinomas lack expression of either marker.     

Clinicopathological features and CD57 expression in renal cell carcinoma in acquired cystic disease of the kidneys: with special emphasis on a relation to the duration of haemodialysis,the degree of calcium oxalate deposition,histological type,and possible tumorigenesis

Enoki Y, Katoh G, Okabe H & Yanagisawa A
(2010) Histopathology 56, 384–394 Clinicopathological features and CD57 expression in renal cell carcinoma in acquired cystic disease of the kidneys: with special emphasis on a relation to the duration of haemodialysis, the degree of calcium oxalate deposition, histological type, and possible tumorigenesis Aims: Acquired cystic disease of the kidney (ACDK) in patients undergoing haemodialysis is known to develop into renal cell carcinoma (RCC), but its pathogenesis remains unclear. The aims were to analyse the histological findings of ACDK‐RCC and to determine its histogenesis. Methods and results: Twenty‐nine RCCs in 23 patients with ACDK were classified into three groups according to the duration of haemodialysis and were analysed for histological type, calcium oxalate (Oxa) deposition, and cyst and atypical cyst (AC) formation. Histologically, 21 tumours were ACDK‐RCC and eight were clear cell carcinoma (CCC). The ratio of ACDK‐RCC and the numbers of cysts and ACs increased as the duration of haemodialysis was prolonged. The degrees of intratumoral Oxa deposition and cyst and AC formation of ACDK‐RCCs were higher than those of CCCs (Oxa, P = 0.028; cyst, P < 0.0001; AC, P = 0.0002). Many ACDK‐RCCs (85.7%) and some CCCs (50%) had characteristics of the thin ascending loop of Henle as assessed by CD57 (HNK‐1) expression, which was rarely expressed in the 29 control cases. Conclusions: ACDK‐RCCs reveal characteristics of Henle’s loop, which may be related to their peculiar pathological features, including intratumoral oxalate deposition and cyst and AC formation.