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High-risk human papillomavirus (HPV) DNA sequences in metaplastic breast carcinomas of Mexican women.

Herrera-Goepfert R, Vela-Chávez T, Carrillo-García A, Lizano-Soberón M, Amador-Molina A, Oñate-Ocaña LF, Hallmann RS - BMC Cancer (2013)

Bottom Line: Mean age of patients with HPV-positive cases was 49 years (range 24-72 years), the same as for HPV-negative cases (range, 30-73 years).There were not striking differences between HPV + and HPV- metaplastic carcinomas regarding clinical findings.Nearly all cases were negative for estrogen, progesterone and Human epidermal growth factor receptor 2 (HER2), but positive for Epidermal growth factor receptor (EGFR).

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, Instituto Nacional de Cancerología México, México, Mexico. rhgoepfert@gmail.com.

ABSTRACT

Background: Metaplastic carcinoma, an uncommon subtype of breast cancer, is part of the spectrum of basal-like, triple receptor-negative breast carcinomas. The present study examined 20 surgical specimens of metaplastic breast carcinomas, for the presence of high-risk Human papillomavirus (HPV), which is suspected to be a potential carcinogenic agent for breast carcinoma.

Methods: Mastectomy specimens from patients harboring metaplastic breast carcinoma, as defined by the World Health Organization (WHO), and who attended the Instituto Nacional de Cancerologia in Mexico City, were retrieved from the files of the Department of Pathology accumulated during a 16-year period (1995-2008). Demographic and clinical information was obtained from patients' medical records. DNA was extracted from formalin-fixed, paraffin-embedded tumors and HPV type-specific amplification was performed by means of Polymerase chain reaction (PCR). Quantitative Real-time (RT) PCR was conducted in HPV positive cases. Statistically, the association of continuous or categorical variables with HPV status was tested by the Student t, the Chi square, or Fisher's exact tests, as appropriate.

Results: High-risk HPV DNA was detected in eight (40%) of 20 metaplastic breast carcinomas: seven (87.5%) HPV-16 and one (12.5%) HPV-18. Mean age of patients with HPV-positive cases was 49 years (range 24-72 years), the same as for HPV-negative cases (range, 30-73 years). There were not striking differences between HPV + and HPV- metaplastic carcinomas regarding clinical findings. Nearly all cases were negative for estrogen, progesterone and Human epidermal growth factor receptor 2 (HER2), but positive for Epidermal growth factor receptor (EGFR).

Conclusions: High-risk HPV has been strongly associated with conventional breast carcinomas, although the subtle mechanism of neoplastic transformation is poorly understood. In Mexican patients, the prevalence of HPV infection among metaplastic breast carcinomas is higher than in non-metaplastic ones, as so the HPV viral loads; notwithstanding, HPV viral loads show wide variation and remain even lower than cervical and other non-cervical carcinomas, making it difficult to assume that HPV could play a key role in breast carcinogenesis. Further studies are warranted to elucidate the meaning of the presence of high-risk HPVDNA in breast carcinomas.

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Human papillomavirus (HPV)-negative metaplastic carcinoma showing a chondroid matrix. (Hematoxylin and eosin stain [H&E]; Original magnification 200×).
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Figure 2: Human papillomavirus (HPV)-negative metaplastic carcinoma showing a chondroid matrix. (Hematoxylin and eosin stain [H&E]; Original magnification 200×).

Mentions: We examined 20 metaplastic breast carcinomas from Mexican female patients, during a 16-year period (1995–2008). Mean age of the patients was 49 years (range, 24–73 years). HPV DNA was detected in eight of 20 (40%) metaplastic breast carcinomas: HPV-16 in seven (87.5%) cases, and HPV-18 in one (12.5%) case of matrix-producing bone carcinoma. Distribution of histological subtypes according to HPV status, is summarized in Table 2 (Figures 1 and 2). Mean age of HPV-positive cases was 49 years (range 24–72 years), with the same mean age for HPV-negative cases (range, 30–73 years). All cases were negative for ER (Figure 3), and all but one HPV-negative carcinoma with squamous differentiation (H-score index: 30), were negative for PgR; 19 cases did not overexpress the HER2 receptor. Following the Hercep Test criteria, the immunoreactions were negative (0) in all but one HPV-positive spindle cell carcinoma, in which a score of 2+ (complete but moderate staining of >10% of tumor cells) was recorded; however, Fluorescence in situ hybridization (FISH) for detecting the gene amplification was not performed. On the other hand, all cases were positive for EGFR 1 (EGFR, ErbB1, HER1) (Figure 4), and all but one carcinoma with chondroid metaplasia, for cytokeratins 5/6. Tumor size ranged from 2 × 2 cm–11.5 × 7cm (mean size 5.4 × 4.1 cm). On taking into account the longer measurement of the tumors, HPV-negative were larger than those HPV-positive metaplastic carcinomas (6.6 vs. 3.7 cm) (p = 0.042). Regardless of its relationship with breast tumors, nine women had previous medical history of at least one cervical smear for screening purposes, as part of the National campaign against carcinoma of the cervix uteri; typical changes of HPV infection appeared in a case of HPV-positive adenosquamous carcinoma, and in one HPV- negative squamous cell/sarcomatoid carcinoma, whereas in the remaining seven cases, the result was reported according to the Bethesda System as negative for intraepithelial lesion or malignancy. Viral loads were constantly low, ranging from 0.02040313 (metaplastic carcinoma with chondroid differentiation)–1.015210939 (metaplastic carcinoma with squamous differentiation) copies/cell (geometric mean, 0.20892 copies/cell), when compared with number of HPV copies/cell in the cell line SiHa (3.985 copies/cell) (Table 3) (Figure 5). Tumor-node-metastasis (TNM) status, age at menarche, menopausal status, relapse, and survival did not show statistically significant differences between HPV-positive and -negative metaplastic carcinomas (Table 4).


High-risk human papillomavirus (HPV) DNA sequences in metaplastic breast carcinomas of Mexican women.

Herrera-Goepfert R, Vela-Chávez T, Carrillo-García A, Lizano-Soberón M, Amador-Molina A, Oñate-Ocaña LF, Hallmann RS - BMC Cancer (2013)

Human papillomavirus (HPV)-negative metaplastic carcinoma showing a chondroid matrix. (Hematoxylin and eosin stain [H&E]; Original magnification 200×).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3852771&req=5

Figure 2: Human papillomavirus (HPV)-negative metaplastic carcinoma showing a chondroid matrix. (Hematoxylin and eosin stain [H&E]; Original magnification 200×).
Mentions: We examined 20 metaplastic breast carcinomas from Mexican female patients, during a 16-year period (1995–2008). Mean age of the patients was 49 years (range, 24–73 years). HPV DNA was detected in eight of 20 (40%) metaplastic breast carcinomas: HPV-16 in seven (87.5%) cases, and HPV-18 in one (12.5%) case of matrix-producing bone carcinoma. Distribution of histological subtypes according to HPV status, is summarized in Table 2 (Figures 1 and 2). Mean age of HPV-positive cases was 49 years (range 24–72 years), with the same mean age for HPV-negative cases (range, 30–73 years). All cases were negative for ER (Figure 3), and all but one HPV-negative carcinoma with squamous differentiation (H-score index: 30), were negative for PgR; 19 cases did not overexpress the HER2 receptor. Following the Hercep Test criteria, the immunoreactions were negative (0) in all but one HPV-positive spindle cell carcinoma, in which a score of 2+ (complete but moderate staining of >10% of tumor cells) was recorded; however, Fluorescence in situ hybridization (FISH) for detecting the gene amplification was not performed. On the other hand, all cases were positive for EGFR 1 (EGFR, ErbB1, HER1) (Figure 4), and all but one carcinoma with chondroid metaplasia, for cytokeratins 5/6. Tumor size ranged from 2 × 2 cm–11.5 × 7cm (mean size 5.4 × 4.1 cm). On taking into account the longer measurement of the tumors, HPV-negative were larger than those HPV-positive metaplastic carcinomas (6.6 vs. 3.7 cm) (p = 0.042). Regardless of its relationship with breast tumors, nine women had previous medical history of at least one cervical smear for screening purposes, as part of the National campaign against carcinoma of the cervix uteri; typical changes of HPV infection appeared in a case of HPV-positive adenosquamous carcinoma, and in one HPV- negative squamous cell/sarcomatoid carcinoma, whereas in the remaining seven cases, the result was reported according to the Bethesda System as negative for intraepithelial lesion or malignancy. Viral loads were constantly low, ranging from 0.02040313 (metaplastic carcinoma with chondroid differentiation)–1.015210939 (metaplastic carcinoma with squamous differentiation) copies/cell (geometric mean, 0.20892 copies/cell), when compared with number of HPV copies/cell in the cell line SiHa (3.985 copies/cell) (Table 3) (Figure 5). Tumor-node-metastasis (TNM) status, age at menarche, menopausal status, relapse, and survival did not show statistically significant differences between HPV-positive and -negative metaplastic carcinomas (Table 4).

Bottom Line: Mean age of patients with HPV-positive cases was 49 years (range 24-72 years), the same as for HPV-negative cases (range, 30-73 years).There were not striking differences between HPV + and HPV- metaplastic carcinomas regarding clinical findings.Nearly all cases were negative for estrogen, progesterone and Human epidermal growth factor receptor 2 (HER2), but positive for Epidermal growth factor receptor (EGFR).

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, Instituto Nacional de Cancerología México, México, Mexico. rhgoepfert@gmail.com.

ABSTRACT

Background: Metaplastic carcinoma, an uncommon subtype of breast cancer, is part of the spectrum of basal-like, triple receptor-negative breast carcinomas. The present study examined 20 surgical specimens of metaplastic breast carcinomas, for the presence of high-risk Human papillomavirus (HPV), which is suspected to be a potential carcinogenic agent for breast carcinoma.

Methods: Mastectomy specimens from patients harboring metaplastic breast carcinoma, as defined by the World Health Organization (WHO), and who attended the Instituto Nacional de Cancerologia in Mexico City, were retrieved from the files of the Department of Pathology accumulated during a 16-year period (1995-2008). Demographic and clinical information was obtained from patients' medical records. DNA was extracted from formalin-fixed, paraffin-embedded tumors and HPV type-specific amplification was performed by means of Polymerase chain reaction (PCR). Quantitative Real-time (RT) PCR was conducted in HPV positive cases. Statistically, the association of continuous or categorical variables with HPV status was tested by the Student t, the Chi square, or Fisher's exact tests, as appropriate.

Results: High-risk HPV DNA was detected in eight (40%) of 20 metaplastic breast carcinomas: seven (87.5%) HPV-16 and one (12.5%) HPV-18. Mean age of patients with HPV-positive cases was 49 years (range 24-72 years), the same as for HPV-negative cases (range, 30-73 years). There were not striking differences between HPV + and HPV- metaplastic carcinomas regarding clinical findings. Nearly all cases were negative for estrogen, progesterone and Human epidermal growth factor receptor 2 (HER2), but positive for Epidermal growth factor receptor (EGFR).

Conclusions: High-risk HPV has been strongly associated with conventional breast carcinomas, although the subtle mechanism of neoplastic transformation is poorly understood. In Mexican patients, the prevalence of HPV infection among metaplastic breast carcinomas is higher than in non-metaplastic ones, as so the HPV viral loads; notwithstanding, HPV viral loads show wide variation and remain even lower than cervical and other non-cervical carcinomas, making it difficult to assume that HPV could play a key role in breast carcinogenesis. Further studies are warranted to elucidate the meaning of the presence of high-risk HPVDNA in breast carcinomas.

Show MeSH
Related in: MedlinePlus