Human breast cancer (BC) is a common tumor in women. Although the incidence of BC has stabilized in recent years,1 BC remains the second cause of cancer death in women.1 Some studies indicate that oncogenic viruses, including Simian Virus 40 (SV40), are involved in the development of BC.2,3 Indeed, SV40 footprints were reported in BC cases 3, while SV40 virions were isolated from an epithelial cell line obtained from the milk of a healthy woman. 4 Recent investigations, based on a specific immunologic assay with synthetic peptides mimicking SV40 viral capsid protein antigens, named mimotopes, revealed that serum samples from normal individuals react with SV40 mimotopes with a prevalence of 18%, 5 while a higher prevalence (26%) was detected in sera from patients affected by malignant pleural mesothelioma (MPM), suggesting an association between SV40 and a subset of MPM. 6 Although many investigations, mainly carried out by PCR techniques, reported SV40 footprints in specimens from normal subjects and oncologic patients, the possible association of SV40 with human BC has not been investigated extensively.7,8 Therefore, we carried out a study to establish whether SV40 antibodies could be detected in a cohort of BC patients. Indirect ELISA testing with specific synthetic peptides derived from SV40 viral capsid proteins were employed as antigens, as recently reported. 5,6 Serum IgG antibodies against SV40 VPs antigens were searched in samples from breast cancer patients (n=78) and paired healthy subjects (n=87) with the same median age (42 ys old). BC samples, tested for reactivity to SV40 epitopes from VP1, B peptide and VP2/3 C peptide 5,6 reached a prevalence of 18% (14/78) and 17% (13/78), respectively. In our study, sera were considered SV40-positive when reacting with both VP1 B and VP2/3 C peptides. The overall prevalence in sera from BC patients by combining SV40-positive samples, both for VP1 B and VP2/3 C peptides, was 15% (12/78). Then, we analyzed the prevalence of SV40 antibodies in normal individuals, who were healthy female blood donors. When tested with the VP1 B peptide, 18/87 sera (21%) of healthy women were positive for SV40 antibodies, whereas 20/87 (23%) were VP2/3 C peptide-positive. The overall prevalence in sera from normal women by combining SV40-positive samples, both for VP1 B and VP2/3 C peptides, was 18%. Thus, the prevalence of SV40-positive sera is higher in the control group than in BC affected patients. The difference in prevalence is not statistically significant (P>0.05). The human peptide hNPS, employed as a negative control antigen, 5,6 did not react with any of the SV40-positive sera. Serologic profile of serum antibody reactivity to SV40 mimotopes indicate that the mean optical density (OD) of BC sera, 0.1518 ± 0.007, was significantly lower, 0.2464 ± 0.023, than that measured in serum samples from healthy women (P < 0.05, Unpaired t test), (Figure). Immunologic data of this investigation indicate that serum antibodies reacted with SV40 VPs antigens only in a subset of BC (15%), but a similar prevalence (18%) was found in a subset of the control, represented by normal female individuals. It should be noted that the low prevalence of SV40 antibodies in serum samples from BC patients is in agreement with an earlier investigation carried out by PCR techniques, which indicated a similar prevalence of SV40 sequences in BC DNA.3 However, in contrast with our results, the same study failed to detect SV40 footprints in normal subjects.3 The similar prevalence of SV40 antibodies in sera from BC affected patients and normal subjects indicates that SV40 infection is not associated with BC. These results suggest that SV40 is simply a passenger not involved in the development of BC.

Breast Cancer and Simian Virus 40 Infection

MARTINI, Fernanda
Primo
;
MAZZONI, Elisa
Secondo
;
CORALLINI, Alfredo;TARONNA, Angelo Pio;QUERZOLI, Patrizia;MAGRI, Eros;MARCI, Roberto;TOGNON, Mauro
Ultimo
2013

Abstract

Human breast cancer (BC) is a common tumor in women. Although the incidence of BC has stabilized in recent years,1 BC remains the second cause of cancer death in women.1 Some studies indicate that oncogenic viruses, including Simian Virus 40 (SV40), are involved in the development of BC.2,3 Indeed, SV40 footprints were reported in BC cases 3, while SV40 virions were isolated from an epithelial cell line obtained from the milk of a healthy woman. 4 Recent investigations, based on a specific immunologic assay with synthetic peptides mimicking SV40 viral capsid protein antigens, named mimotopes, revealed that serum samples from normal individuals react with SV40 mimotopes with a prevalence of 18%, 5 while a higher prevalence (26%) was detected in sera from patients affected by malignant pleural mesothelioma (MPM), suggesting an association between SV40 and a subset of MPM. 6 Although many investigations, mainly carried out by PCR techniques, reported SV40 footprints in specimens from normal subjects and oncologic patients, the possible association of SV40 with human BC has not been investigated extensively.7,8 Therefore, we carried out a study to establish whether SV40 antibodies could be detected in a cohort of BC patients. Indirect ELISA testing with specific synthetic peptides derived from SV40 viral capsid proteins were employed as antigens, as recently reported. 5,6 Serum IgG antibodies against SV40 VPs antigens were searched in samples from breast cancer patients (n=78) and paired healthy subjects (n=87) with the same median age (42 ys old). BC samples, tested for reactivity to SV40 epitopes from VP1, B peptide and VP2/3 C peptide 5,6 reached a prevalence of 18% (14/78) and 17% (13/78), respectively. In our study, sera were considered SV40-positive when reacting with both VP1 B and VP2/3 C peptides. The overall prevalence in sera from BC patients by combining SV40-positive samples, both for VP1 B and VP2/3 C peptides, was 15% (12/78). Then, we analyzed the prevalence of SV40 antibodies in normal individuals, who were healthy female blood donors. When tested with the VP1 B peptide, 18/87 sera (21%) of healthy women were positive for SV40 antibodies, whereas 20/87 (23%) were VP2/3 C peptide-positive. The overall prevalence in sera from normal women by combining SV40-positive samples, both for VP1 B and VP2/3 C peptides, was 18%. Thus, the prevalence of SV40-positive sera is higher in the control group than in BC affected patients. The difference in prevalence is not statistically significant (P>0.05). The human peptide hNPS, employed as a negative control antigen, 5,6 did not react with any of the SV40-positive sera. Serologic profile of serum antibody reactivity to SV40 mimotopes indicate that the mean optical density (OD) of BC sera, 0.1518 ± 0.007, was significantly lower, 0.2464 ± 0.023, than that measured in serum samples from healthy women (P < 0.05, Unpaired t test), (Figure). Immunologic data of this investigation indicate that serum antibodies reacted with SV40 VPs antigens only in a subset of BC (15%), but a similar prevalence (18%) was found in a subset of the control, represented by normal female individuals. It should be noted that the low prevalence of SV40 antibodies in serum samples from BC patients is in agreement with an earlier investigation carried out by PCR techniques, which indicated a similar prevalence of SV40 sequences in BC DNA.3 However, in contrast with our results, the same study failed to detect SV40 footprints in normal subjects.3 The similar prevalence of SV40 antibodies in sera from BC affected patients and normal subjects indicates that SV40 infection is not associated with BC. These results suggest that SV40 is simply a passenger not involved in the development of BC.
2013
Martini, Fernanda; Mazzoni, Elisa; Corallini, Alfredo; Taronna, Angelo Pio; Querzoli, Patrizia; Magri, Eros; Marci, Roberto; R., Dolcetti; G., Rezza; G., Barbanti Brodano; Tognon, Mauro
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/1770499
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 12
  • ???jsp.display-item.citation.isi??? 12
social impact