Study of matrix metalloproteinases and their tissue inhibitors in ductal in situ carcinomas of the breast.

AIMS: To analyse the expression of metalloproteinases (MMPs) and their inhibitors (TIMPs) in ductal carcinoma in situ of the breast (DCIS). METHODS AND RESULTS: An immunohistochemical study was performed in 56 patients with pure DCIS, in 39 with DCIS adjacent to invasive carcinoma (IDC) and 63 patients with T1 IDC, using tissue microarrays and specific antibodies against MMPs and TIMPs. Immunohistochemical results were categorized using a specific software program. The data were analysed by unsupervised hierarchical cluster analysis by each cellular type. IDC showed a higher expression rate of MMP-7 and TIMP-1 than pure DCIS, as well as a higher expression rate of MMP-9 and TIMP-3 than the DCIS component of mixed cases, whereas pure DCIS showed a higher rate of expression of MMP-9 and -11 and TIMP-3 than in the DCIS component of mixed cases. Pure DCIS with a periductal inflammatory infiltrate showed significantly higher MMP-2, -14 and TIMP-1. Dendograms identified two cluster groups with distinct MMP/TIMP expression profiles in neoplastic cells and fibroblastic or mononuclear inflammatory cells surrounding the neoplastic ducts of pure DCIS. CONCLUSIONS: The results indicate the distinct variability in MMP/TIMP expression by DCIS, which may be of potential biological and clinical interest in breast cancer.

Overexpression of matrix metalloproteinases and their inhibitors in mononuclear inflammatory cells in breast cancer correlates with metastasis-relapse.

An immunohistochemical study was performed using tissue microarrays and specific antibodies against matrix metalloproteinase (MMP)-1, -2, -7, -9, -11, -13 and -14, tissular inhibitors of metalloproteinase (TIMP)-1, -2 and -3. More than 2600 determinations on cancer specimens from 131 patients with primary ductal invasive tumours of the breast were performed. To identify specific groups of tumours with distinct expression profiles the data were analysed by unsupervised hierarchical cluster analysis by each cellular type. We did not find well-defined cluster of cases for tumour cells or fibroblastic cells. However, for mononuclear inflammatory cells the dendogram shows a first-order division of the tumours into two distinct MMP/TIMP molecular profiles, designated group 1 (n=89) and group 2 (n=42). Matrix metalloproteinase-7, -9, -11, -13 and -14, and TIMP-1 and -2, were identified as showing significant high expression in group 2 compared with group 1. Multivariate analysis demonstrated that clustering for mononuclear inflammatory cells was the most potent independent factor associated with distant relapse-free survival (group 2: 5.6 (3.5-9.6), P<0.001). We identify a phenotype of mononuclear inflammatory cells infiltrating tumours, which is associated with the development of distant metastasis. Therefore, this finding suggests that these host inflammatory cells could be a possible target for inhibition of metastasis.

Study of matrix metalloproteinases and their inhibitors in breast cancer.

An immunohistochemical study was performed using tissue microarrays and specific antibodies against matrix metalloproteinases (MMPs) 1, 2, 7, 9, 11, 13, 14, and their tisullar inhibitors (TIMPs) 1, 2, and 3. More than 2600 determinations on cancer specimens from 131 patients with primary ductal invasive tumours of the breast (65 with and 66 without distant metastasis) and controls were performed. Staining results were categorised using a score based on the intensity of the staining and a specific software program calculated the percentage of immunostained cells automatically. We observed a broad variation of the total immunostaining scores and the cell type expressing each protein. There were multiple and significant associations between the expression of the different MMPs and TIMPs evaluated and some parameters indicative of tumour aggressiveness, such as large tumour size, advanced tumour grade, high Nottinham prognostic index, negative oestrogen receptor status, peritumoural inflammation, desmoplastic reaction, and infiltrating tumoural edge. Likewise, the detection of elevated immunohistochemical scores for MMP-9, 11, TIMP-1, and TIMP-2, was significantly associated with a higher rate of distant metastases. The expression of MMP-9 or TIMP-2 by tumour cells, MMP-1, 7, 9, 11, 13, or TIMP-3 by fibroblastic cells, and MMP-7, 9, 11, 13, 14, TIMP-1, or TIMP-2 by mononuclear inflammatory cells, was also significantly associated with a higher rate of distant metastases.

Pronóstico del cáncer de cérvix en un hospital de área / Prognostic factors and outcome of cervical cancer in a district hospital

Objetivo: Analizar las características clinicopatológicas de las pacientes diagnosticadas de cáncer invasivo de cérvix en nuestro ámbito clínico, así como su evaluación pronóstica. Sujetos y métodos: Estudio retrospectivo observacional de todas las pacientes con diagnóstico histológico de cáncer invasivo de cérvix en nuestro servicio hospitalario durante el período 1994-2003. Se recogen las características clínicas de las pacientes y de los tumores. Se establecen las curvas de supervivencia según el método de Kaplan-Meier y se comparan mediante la prueba de rangos logarítmicos para el análisis univariante. El análisis multivariante se realizó mediante la regresión de Cox. Resultados: Se identificaron 39 pacientes con una media de edad de 54 años. La mayoría presentaba metrorragias y se encontraba en un estadio inicial (66%) en el momento del diagnóstico. El 84% de los tumores fueron escamosos, moderadamente diferenciados (56%) y sin invasión linfovascular (87%). El tratamiento fue preferentemente radioterapéutico (48%). Los factores pronósticos para la supervivencia global fueron el estadio clínico (p < 0,001), el valor de hemoglobina (p = 0,007) y el grado histológico (p = 0,01). Sólo el estadio se mantuvo como factor pronóstico independiente (p = 0,001) en el análisis multivariante. Conclusiones: Nuestros resultados resaltan la importancia de un diagnóstico precoz del cáncer de cérvix

Objective: To analyze the clinical and pathologic characteristics of invasive cervical cancer in our center and to identify prognostic factors. Subjects and methods: We performed an observational, retrospective study of all women with a histopathological diagnosis of invasive cervical cancer in our department between 1994 and 2003. Clinical and tumoral characteristics were included. Survival curves were calculated with the Kaplan-Meier method and were compared with the log rank test. Multivariate analysis was performed using the Cox regression model. Results: Thirty-nine patients were identified. The mean age was 54 years. At diagnosis, most of the patients showed abnormal bleeding and initial-stage tumors (66%). Thirty-three tumors (84%) were squamous, 22 were moderately differentiated (56%) and 34 showed no lymphovascular invasion (87%). The most frequent treatment was radiotherapy (48%). Prognostic factors for overall survival were clinical stage (p < 0.001), pre-treatment hemoglobin levels (p = 0.007) and histologic grade (p = 0.01). The only independent prognostic factor in the multivariate analysis was clinical stage. Conclusions: Our results emphasize the importance of an early diagnosis in invasive cervical cancer

[Clinical significance of tumor content of epidermal growth factor receptor in breast cancer]. / Significación clínica del contenido tumoral del receptor del factor de crecimiento epidérmico en el cáncer de mama.

OBJECTIVE: To determine the content of epidermal growth factor receptor (EGFR) using a radioligand method in breast cancer and to analyze the relationship between the EGFR levels and the characteristics of patients and tumors. Prognostic significance was also analyzed. MATERIAL AND METHODS: EGFR was measured by a single point radioligand assay in 265 invasive breast carcinomas tissues. In addition, estrogen and progesterone receptors (ER and PR) were measured by enzymatic immunoassays. We analyze the relationship of EGFR levels with the different clinico-pathologic parameters. RESULTS: EGFR levels in breast carcinomas varied widely (0.1 to 403) with a median at 4 fmol/mg prot. The significantly higher concentrations of EGFR were detected in patients under 60 years old (p = 0.042), undifferentiated tumors (p = 0.04), and carcinomas with negative ER and PR (p < 0.019 y p < 0018, respectively). In addition, there was a negative correlation between EGFR and the ER and PR levels (p < 0.05). EGFR levels did not show any relationship with the patient's prognosis. CONCLUSIONS: In addition, intratumoral levels of EGFR in breast carcinomas vary widely and the highest concentrations are associated with the most aggresive characteristics of the tumor.

Aspartil-proteasas y cáncer de mama / Aspartyl-proteases and breast cancer

Las aspartil-proteasas son un conjunto de enzimasproteolíticas ampliamente distribuidas por el organismo humano, donde desempeñan funciones fisiológicas muy variadas, además de estar implicadas en diferentes procesos patológicos. La catepsina D (Cat D), el pepsinógeno C (pep C) y la GCDFP-15, son tres as-partil-proteasas que han sido implicadas en la patologíamamaria. La Cat D se localiza normalmente en los lisosomas de todas las células del organismo y se relaciona con el catabolismo proteico celular. Su expresión en el cáncer de mama se ha propuesto como marcador de dependencia estrogénica, como factor de crecimiento y como proteasa importante involucrada en la invasión tumoral. Sin embargo, la información existente sobre su valor pro-nóstico en esta neoplasia resulta algo conflictiva. Por otra parte, existen datos que sugieren la presencia de Cat D en las secreciones mamarias podría representar un marcador biológico de transformación maligna. El Pep C es una enzima normalmente involucrada en la digestión de proteínas en el estómago y de expresión muy restringida en el resto de los tejidos del organismo humano. Sin embargo, se ha observado que el epitelio de los quistes de mama y un porcentaje significativo de carcinomas de mama expresan esta aspartil-proteasa. Además, también se ha demostrado que la expresión de Pep C por los carcinomas de mama representa un nue-vo factor pronóstico de evolución favorable, así comoun posible marcador de una vía específica de respuesta hormonal en estos tumores. La GCDFP-15 es un componente proteico mayoritariodel fluido quístico de la enfermedad macroquística de la mama y de la secreción mamaria obtenida a través del pezón de la mayoría de las mujeres no lactantes. Esta proteasa es también expresada por un porcentaje eleva-do de carcinomas mamarios, en los cuales representa un marcador de diferenciación apocrina y un posiblemarcador biológico de respuesta hormonal androgénica (AU)

Importancia de la edad como factor pronóstico determinante de la variabilidad de las características clínico-patológicas de las pacientes con cáncer de mama / Importance of the age as factor determining prognosis of the variability of the clinical-pathological characteristics of patients with breast cancer

Objetivo: analizar la importancia de la edad como factor pronóstico en el cáncer de mama, lo cual podría tener importantes implicaciones en el tratamiento y manejo clínico de las pacientes. Material y métodos: estudio retrospectivo de 769 pacientes intervenidas quirúrgicamente por cáncer de mama (1983-1999). El tiempo medio de seguimiento fue de 34,4 meses. Se realizaron estudios bioquímicos para la determinación de receptores de estrógenos y progesterona, contenido de ADN y fase S. Resultados: la edad media de las 769 pacientes fue de 59 años, y la década de mayor presentación del cáncer de mama fue la de los 50 años (26,5 per cent). Encontramos una asociación estadísticamente significativa entre la edad de las pacientes y el tamaño tumoral (p<0,0001), grado histológico (p<0,018), contenido de receptores de estrógenos (p<0,014) y fase S (p<0,019). Las pacientes de menor edad tuvieron un mayor número de casos de tumores de menor ta maño, histológicamente menos diferenciados y con receptores estrogénicos negativos. El análisis univariante demostró que el mayor tamaño tumoral, el estadio nodal positivo y el grado histológico indiferenciado de los tumores estuvieron significativa y positivamente asociados con un menor tiempo libre de enfermedad y supervivencia total de las pacientes. Sin embargo, no existieron diferencias significativas en el pronóstico entre los diferentes grupos de pacientes clasificadas en función de sus distintas edades. Conclusiones: el presente estudio demuestra diferencias en las características clínicas, morfológicas y biológicas de los carcinomas mamarios en función de la edad de las pacientes. Sin embargo , nuestros resultados no demostraron diferencias significativas en el pronóstico de las pacientes en función de su edad. Ello podría tener importantes implicaciones de cara al tratamiento y manejo clínico de las pacientes, principalmente de aquellas de más avanzada edad (AU)

Expresión y significación clínica del pepsinógeno c y la colagenasa-3 en el carcinoma de endometrio / Expression and clinical significance of pepsinogen C and collagenase-3 in endometrial carcinoma

Objetivo: Analizar la expresión tumoral del pepsinógeno C y de la colagenasa-3 en el adenocarcinoma de endometrio y la relación con las características de las pacientes y de sus tumores.Sujetos y métodos: Analizamos retrospectivamente mediante análisis inmunohistoquímico, utilizando anticuerpos monoclonales, 58 pacientes diagnosticadas y tratadas de adenocarcinoma de endometrio.Resultados: Se detectó pepsinógeno C en 21 tumores (36 por ciento) y colagenasa-3 en 30 (51 por ciento). La expresión de estas proteínas se asoció significativamente con la profundidad de la invasión miometrial, de forma que a mayor invasión del miometrio, menor expresión de pepsinógeno C y mayor de colagenasa-3 (p < 0,005 y p < 0,02, respectivamente). El análisis combinado de ambas enzimas proteolíticas predijo significativamente el grado de invasión miometrial (p < 0,001).Conclusión: Un porcentaje significativo de adenocarcinomas de endometrio expresan pepsinógeno C y colagenasa-3, lo cual refleja un comportamiento biológico diferente, y pueden ser útiles en la predicción preoperatoria de la invasión miometrial en el cáncer de endometrio (AU)

[Analysis of the cytosolic content of the pS2 protein in breast cancer]. / Análisis del contenido citosólico de la proteína pS2 en el cáncer de mama.

OBJECTIVE: To analyze pS2 cytosolic levels in breast carcinomas and their correlation with different clinical characteristics of the patients and their tumours. MATERIAL AND METHODS: Cytosolic pS2 levels were measured by radioimmunometric assay in tumours from 168 breast cancer patients. RESULTS: The pS2 values ranged from 0 to 251 ng/mg protein (mean SD: 21.8 38.1; median: 7.9 ng/mg protein). These protein levels were significantly (p < 0.05) higher in premenopausal patients (27.6 45.2) than in postmenopausal patients (19.5 33.8). Intratumour pS2 levels were also significantly (p < 0.05) correlated with histologic grade of the tumours, and were higher in well diferentiated tumours (grade I: 28.8 42.8) than in moderately differentiated tumours (grade II: 19.7 35.6) and than in poorly differentiated tumours (grade III: 18.9 37.3). Similarly, significant differences in pS2 content were found between positive estrogen receptor (ER) tumours and ER-negative tumours (29.1 46.5 vs 11.3 15.9, respectively; p<0.0001), as well as between positive progesterone receptor (PR) tumours and PR-negative tumours (29.1 49.8 vs 15.3 21.5, respectively; p < 0.05). CONCLUSIONS: The results suggest that pS2 may be a useful prognostic marker in breast cancer, and may also be useful to identify patients who are likely to benefit from hormone therapy.

Análisis del contenido citosólico de la proteína ps2 en el cáncer de mama / Analysis of the cytosolic content of the ps2 protein in breast cancer

Objetivo: Analizar los niveles citosólicos de pS2 en carcinomas de mama y su correlación con las diferentes características clínicas de las pacientes y de sus tumores.Material y métodos: Se determinaron por método inmunorradiométrico los niveles citosólicos de pS2 en 168 tumores de pacientes con cáncer de mama. Resultados: Los valores de pS2 variaron de 0 a 251 ng/mg proteína (media ñ DE: 21,8 ñ 38,1; mediana: 7,9 ng/mg proteína). Esos niveles de la proteína fueron significativamente (p < 0,05) más elevados en las pacientes premenopáusicas (27,6 ñ 45,2) que en las pacientes postmenopáusicas (19,5 ñ 33,8). Los niveles intratumorales de pS2 también estuvieron significativamente (p < 0,05) correlacionados con el grado histológico de los tumores, siendo más elevados en los tumores bien diferenciados (grado I: 28,8 ñ 42,8) que en los tumores moderadamente diferenciados (grado II: 19,7 ñ 35,6) y que en los tumores pobremente diferenciados (grado III: 18,9 ñ 937,3). Similarmente, se encontraron diferencias significativas en el contenido de pS2 entre los tumores receptor de estrógeno (RE)-positivos y los tumores RE-negativos (29,1 ñ 46,5 vs 11,3 ñ 15,9, respectivamente; p < 0,0001), así como también entre los tumores receptor de progesterona (RP)-positivos y los tumores RP-negativos (29,1 ñ 49,8 vs 15,3 ñ 21,5, respectivamente; p < 0,05). Conclusión: Estos resultados sugieren que la pS2 puede ser un útil marcador pronóstico en el cáncer de mama, así como también para identificar pacientes que pueden beneficiarse de terapia hormonal (AU)

Lysozyme expression by breast carcinomas, correlation with clinicopathologic parameters, and prognostic significance.

BACKGROUND: Here we evaluate the expression and prognostic value of lysozyme, a milk protein that is also synthesized by a significant percentage of breast carcinomas, in women with breast cancer. METHODS: Lysozyme expression was examined by immunohistochemical methods in a series of 177 breast cancer tissue sections. Staining was quantified by using the HSCORE system, which considers both the intensity and the percentage of cells staining at each intensity. The prognostic value of lysozyme was retrospectively evaluated by multivariate analysis that took into account conventional prognostic factors. RESULTS: A total of 126 of 177 carcinomas (69.4%) stained positive for this protein, but there were clear differences among them with regard to the intensity and percentage of stained cells. Lysozyme values were higher in well-differentiated and moderately differentiated tumors than in poorly differentiated tumors (P < .05). Similarly, lysozyme levels were higher in small and node-negative tumors than in large and node-positive tumors (P < .05). Moreover, results indicated that low lysozyme content predicted shorter relapse-free survival and overall survival (P < .005). Separate Cox multivariate analysis in subgroups of patients as defined by node status showed that lysozyme expression was an independent prognostic factor able to predict both relapse-free survival and overall survival in node-negative patients (P < .05). CONCLUSIONS: Tumoral expression of lysozyme is associated with lesions of favorable evolution in breast cancer. This milk protein may be a new prognostic factor in patients with breast cancer.

Apolipoprotein D expression in endometrial carcinomas.

BACKGROUND: Apolipoprotein D is a protein component of the human plasma lipid transport system but is also associated with a more favorable prognosis in breast cancer and ovarian cancer women. This study was undertaken to examine the tumoral expression of apolipoprotein D in endometrial cancer and to analyze the possible correlation with tumor and patients characteristics as well as androgen receptors and its prognostic significance. METHODS: Immunohistochemical evaluation was used to examine apolipoprotein D expression in paraffin blocks from 58 endometrial carcinomas. RESULTS: A total of twenty (34%) tumors stained positively. Staining was localized in tumor cells. No significant correlation was found between apo D expression and patients or tumor characteristics and androgen receptor status. In addition, apolipoprotein D expression was not associated with patient prognosis. CONCLUSIONS: Apolipoprotein D is expressed by a significant percentage of endometrial carcinomas without apparent association with other clinicopathologic parameters or with outcome of patients.

Significación clínica de la apariencia mamográfica de los carcinomas mamarios / Clinical significance of the mammographic appearance of breast carcinoma

Objetivo. En este estudio analizamos la relación entre la apariencia mamográfica de los carcinomas mamarios y las características de las pacientes y sus tumores, así como el posible valor pronóstico de los hallazgos mamográficos. Método. Realizamos un estudio retrospectivo sobre 237 pacientes diagnosticadas y tratadas por carcinoma ductal infiltrante de mama entre los años 19841994. El tiempo medio de seguimiento fue de 33,9 meses. Los tumores se clasificaron en cinco grupos diferentes según su apariencia mamográfica: espiculados con o sin microcalcificaciones (tipo A), difuso (tipo B), microcalcificaciones sin una masa evidente (tipo C), clrcunscrito (tipo D) y no visible en mamografía (tipo E). Además, se evaluó independientemente el significado clínico de la existencia de microcalcificaciones. Resultados. La apariencia radiográfica tipo A se detectó en 125 pacientes (52,7 por ciento), el tipo B en 24 (10,1 por ciento), el tipo C en 32 (13,5 por ciento), el tipo D en 49 (20,7 por ciento) y el tipo E en siete pacientes (2,9 por ciento). Por otra parte, un total de 87 tumores (36,7 por ciento) mostró microcalcificaciones. Hubo diferencias significativas en la distribución de estos tipos mamográficos según el estado menopáusico, la afectación ganglionar y el grado histológico de los tumores. Así, el porcentaje de tumores tipo A fue más alto en tumores sin afectación ganglionar y en aquellos bien diferenciados. Por el contrario, el tipo B se detectó en un alto porcentaje de tumores con ganglios positivos y en los pobremente diferenciados. Además, las microcalcificaciones se asociaron significativamente con tumores pequeños y con ganglios negativos. Finalmente, el análisis multivariante demostró que el tipo B y la ausencia de microcalcificaciones se asociaban significativamente a un alto riesgo de recurrencia y fallecimiento. Conclusión. Estos resultados nos inducen a considerar que la apariencia mamográfica de los carcinomas mamarios puede reflejar su comportamiento biológico (AU)

Análisis de la expresión del pepsinógeno C en metástasis ganglionares de carcinoma de mama / Analysis of pepsinogen C expression in lymph node metastases of breast cancer

En este estudio analizamos en los tumores primarios y en ganglios axilares metastásicos de 30 mujeres con cáncer de mama, mediante análisis inmunohistoquímico, la expresión tumoral del pepsinógeno C, una proteína normalmente expresada por la mucosa gástrica. De los tumores mamarios primarios, 16 (53,3 por ciento) mostraron una tinción inmunohistoquímica positiva para el pepsinógeno C, mientras que 17 (56,6 por ciento) lo hicieron en sus ganglios linfáticos tumorales. Además existió una relación significativamente positiva entre la expresión tumoral de pepsinógeno C en los tumores primarios y los ganglios metastásicos (p < 0,002). Sin embargo, sólo la expresión tumoral de esa proteína en los tumores primarios alcanzó significación estadística (p < 0,05) como factor pronóstico de evolución favorable para predecir la supervivencia de las pacientes. (AU)

Comparative study of two androgen-induced markers (apolipoprotein D and pepsinogen C) in female and male breast carcinoma.

BACKGROUND: Male breast cancer (MBC) is a rare tumor in comparison to the same disease in the female population (FBC). Classical prognostic factors (tumor size, node status, estrogen receptor positivity, histological grade) have a similar prognostic value in both tumors, but MBC seems to have a worse outcome. Several markers under estrogen control have been shown with a similar incidence in breast tumors of both sexes, while androgen-induced markers have been detected in a higher percentage of breast tumors in males. AIMS AND METHODS: Our purpose was to compare in 68 MBC and in 68 FBC the expression of Pepsinogen C (Pep C) and Apolipoprotein D (Apo D), two proteins under androgen control, by immunohistochemical methods. RESULTS: Pep C was expressed by 52 of 68 (76.4%) MBC patients, whereas 34 of 68 (50%) FBC showed positive staining. Apo D was expressed by 57 of 68 (83.8%) MBC patients, while 40 of 68 (41.2%) FBC stained positively. Differences between percentages of positive expression were significant (p<0.005 for Pep C; p<0.0001 for Apo D). Moreover, differences between expression levels of Pep C and Apo D in both populations of patients were significant. The mean value of Pep C was significantly higher in male breast tumors (HSCORE = 141.3) than in the females (HSCORE = 80.3) (p<0.0001). Similarly, Apo D mean value was significantly higher in MBC (HSCORE = 161.5) than in FBC (HSCORE = 102.3) (p=0.006). CONCLUSION: These differences can open the field of a more selective hormonal therapy that should not be based on estrogen receptor status only, but also on androgen receptor status.

Apolipoprotein D expression in metastasic lymph nodes of breast cancer.

BACKGROUND: Apolipoprotein D is a glycoprotein of the human plasma whose functional role remains unclear. On the other hand, this protein is also produced by breast carcinomas and is positively associated with a favorable outcome of patients. However, none study has focused on metastasic lesions. AIM: To analyze apolipoprotein D expression in breast cancer patients and their synchronous metastasic axillary lymph nodes. METHODS: We analyzed by immunohistochemical assay both, the tumoral expression of apolipoprotein D in primary tumors and in their synchronous metastasic axillary lymph nodes of 30 node-positive breast cancer patients. RESULTS: Of the primary tumors, 28 (93.3%) showed a positive immunostaining for apolipoprotein D, although there was wide variability immunostaining values. On the other hand, 16 (53.3%) patients showed a positive immunostaining for the protein in their tumoral lymph nodes. In addition, there was a significant positive relationship between the tumoral expression of apolipoprotein D in primary tumors and metastasic lymph nodes (P < 0.05). However, only immunostaining values of the protein in primary tumors achieve statistical signification (P < 0.05) as prognostic factor of favorable evolution to predict overall survival from patients. CONCLUSIONS: Apolipoprotein D is also expressed in metastasic lymph nodes of breast carcinomas, but with a different pattern of immunostaining and less clinical significance than in primary tumors.

Expression and clinical significance of apolipoprotein D in male breast cancer and gynaecomastia.

BACKGROUND: Apolipoprotein D (Apo D) is a protein component of the human plasma lipid transport system which is present in benign and malignant human breast tissues. This study analysed the expression of Apo D in men with gynaecomastia or breast cancer, and evaluated its use as a prognostic marker in breast cancer. METHODS: Immunohistochemical expression of Apo D was examined in specimens from 15 men with gynaecomastia, two with in situ breast carcinoma and 68 with invasive male breast cancer. Median follow-up in patients with breast cancer was 44 months. RESULTS: All gynaecomastia specimens, both in situ carcinomas and 57 invasive carcinomas (84 per cent) stained positively for Apo D. Apo D values were significantly correlated with axillary node involvement and histological grade of the tumours. In men with breast cancer univariate analysis showed a statistical association between node status and Apo D content with relapse-free survival (P < 0.001) and overall survival (P < 0.05). Cox multivariate analysis showed that Apo D was a significant indicator of relapse-free survival (P = 0. 0089), but node status was the strongest factor able to predict both relapse-free (P = 0.0336) and overall (P = 0.0346) survival. CONCLUSION: Apo D was expressed in gynaecomastia and a high percentage of male breast carcinomas. There was a positive association of Apo D content in male breast tumours with favourable outcome. Apo D expression was a significant independent indicator of relapse-free survival in male breast cancer.